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1  with one another and with experimental data difficult.
2 tion of protein structural ensembles remains difficult.
3 ting privacy in family-based studies is more difficult.
4 etermining its behavioral impact have proven difficult.
5 re, direct measurement of the LBHB energy is difficult.
6 stematic analysis of such data unnecessarily difficult.
7 rformance outcomes under untested conditions difficult.
8 ed clinical trials) blinding is usually more difficult.
9  its role in the pathogenesis of PD has been difficult.
10 oughput screening conditions is particularly difficult.
11  paCOS with patterns of interest have proven difficult.
12 the liver in live model organisms has proven difficult.
13 n humans and other great apes is notoriously difficult.
14 ss on the detailed study of satDNA structure difficult.
15 fying the relative success of the two can be difficult.
16 e manipulation within defined cells has been difficult.
17 ucidation of microbe-microbe interactions is difficult.
18 akes species-specific diagnosis of infection difficult.
19 otein-ligand complexes, which is notoriously difficult.
20  compounds with improved permeability can be difficult.
21  many uncertainties that make drug discovery difficult.
22 resolution makes accurate placement of atoms difficult.
23 e make detection of these rare variants very difficult.
24 on sequencing (NGS) data for analysis can be difficult.
25 ity level, making provision of interventions difficult.
26 ntation of multilocus model in GWAS is still difficult.
27 s to the functional Env entry unit extremely difficult.
28 n soft actuators with high strain density is difficult.
29 ons) and sleep-dependent plasticity has been difficult.
30 m these noisy high-throughput screens remain difficult.
31 f anthropogenic and natural sources remained difficult.
32 direct comparison of different study-results difficult and calls for standardized models.
33 producible doping with high concentration is difficult and carrier lifetime is low.
34  subcellular fractionation is experimentally difficult and low throughput.
35        The treatment of a PSH is notoriously difficult and recurrences up to 20% have been reported d
36 ating chemical and physical contributions is difficult and requires multiple controls.
37 ir implementation into synthetic collagen is difficult and requires the replacement of the canonical
38                  Tuning them properly may be difficult and, typically, based on a trial-and-error app
39            The melanoma recognition is still difficult, and generally, relies on subjective assessmen
40 of endosomal dynamics in live cells remained difficult as these structures lie at or below the 250 n
41 , isolation of an electrogenic strain proved difficult as transfer cultures failed to grow after mult
42  or asthma due to gastroesophageal reflux is difficult, as no criterion standard test exits.
43 cluster model, we labelled the clusters as: "Difficult asthma" (n = 132); "Early-onset mild atopic" (
44 ignificantly diminished among children with "Difficult asthma"; blood eosinophilia was a significant
45 mpetus to their evaluation and management in difficult asthma.
46                    But this is prohibitively difficult at experimental level.
47 on of species and ecosystems is increasingly difficult because anthropogenic impacts are pervasive an
48 rburg virus (MARV) and Ravn virus (RAVV), is difficult because of substantial sequence variability.
49          However, studying them in detail is difficult because of the extreme conditions (high pressu
50 ting benefit for individual patients remains difficult because of the heterogeneity in treatment resp
51 terrelated at the single-cell level has been difficult because of the lack of techniques for multimod
52 , a physical realisation of these devices is difficult because of their reliance on a clock.
53              Analysis of constitutive CME is difficult because the initiation of endocytic events is
54 c) mutations for Mendelian disorders is more difficult, because of the abundance of benign heterozygo
55                                 Treatment is difficult, because of the localization and the invasiven
56 mple building blocks remains one of the most difficult challenges in chemistry.
57 cting groups at C17-OH and C18-OH have posed difficult challenges.
58 ough multiple RETs facilitating an otherwise difficult chemical process.
59 de an enzyme's active site to allow slow and difficult chemical reactions to occur so rapidly?
60 atients, families and themselves; and having difficult conversations.
61 nsfer protein) inhibitors has had a long and difficult course with 3 compounds failing in phase III c
62  increase sampling times and performance for difficult discriminations, arguing for temporal integrat
63 entification using morphological criteria is difficult due the plasticity of these characteristics an
64 transplantation, systemic anticoagulation is difficult due to bleeding.
65 he full-length structure of NEMO have proved difficult due to its apparent high conformational plasti
66 g the TP domain for antiviral development is difficult due to the lack of homology to other proteins
67                                 Diagnosis is difficult due to the ongoing systemic inflammatory respo
68              Unfortunately, diagnosis can be difficult, due to numerous mimics, and to the absence of
69 d eosinophilia was a significant feature of "Difficult," "Early-onset mild atopic," and "Late-onset a
70  making comprehensive detection of mutations difficult, especially at early stages of cancer.
71  to structural models complementary to often-difficult experimental methods.
72 eous abortion (OR, 0.11; 95% CI, 0.02-0.53), difficult fetal transition (bradycardia [OR, 15.0; 95% C
73 t forms of physical activity is particularly difficult for both the individual with type 1 diabetes a
74 new phenotypes serve as secret tags that are difficult for defector to discover and chase after.
75                          Measurement is more difficult for dynamic contact angles, for which theoreti
76 uates in intensity over time is particularly difficult for hearing-impaired listeners with a sensorin
77 l biology and genetics of spermatogenesis is difficult for most species because it occurs within a co
78 make analysis and prioritization of variants difficult for researchers with limited bioinformatics sk
79                         This is particularly difficult for samples containing fungal mycelia, where p
80        Our measurements show that it is more difficult for the flies to escape from Mono Lake water t
81 are tools, training materials etc.) makes it difficult for users to find them.
82 differences in experimental protocols, it is difficult, if not impossible, to make meaningful compari
83 ification of direct regulatory mechanisms is difficult in animals or primary adipocytes due to these
84 of TiO2, a promising photocatalyst, has been difficult in both powder and thin-film forms due to the
85 r spatial imaging of the 3D fields, which is difficult in high-energy physics and cosmology.
86                    However, the diagnosis is difficult in low prevalence areas because of a low index
87 key clinical examination technique have been difficult in neurology residency training.
88 ansport, deposition, and processing has been difficult, in contrast to the well-characterized genes i
89 trogen loading, predicting emissions remains difficult, in part due to challenges in disentangling di
90 fine particle systems is a long standing and difficult inverse problem.
91 s ends and where jamming begins becomes very difficult or even impossible.
92      Validating HSP72 inhibitors in cells is difficult owing to competition with the high affinity an
93           alpha has historically been a very difficult parameter to measure with reported values vary
94 on of eosinophilic esophagitis (EoE) remains difficult, particularly the assessment of the patient's
95  transanal technique pioneered to facilitate difficult pelvic dissections.
96 ies (bNAbs) for ebolaviruses is possible but difficult, potentially due to the rarity of bNAb clones
97 nd execute scientific experiments to solve a difficult problem in genetics.
98                        Another important and difficult problem is the discovery of molecular disease
99      Sphinx can be used successfully for the difficult problem of antibody H3 prediction, outperformi
100 ll integrate to reach a desired outcome is a difficult problem that has been studied in great detail
101 al pair due to their utility for solving the difficult protein folding problem.
102 ay be applicable to crystallization of other difficult protein targets, as well as to other crystalli
103 in types of adulterants make their detection difficult, so that food authentication often poses a cha
104 lly demanding and recognizing novel folds is difficult such that the majority of proteins have not be
105  surgical complications and/or inadequate or difficult symptom management.
106 al Review also tries to exemplarily show how difficult synthetic and theoretical problems can eventua
107 covalent bonding in-arguably-one of the most difficult systems to study, the Am-Cl interaction within
108 ritize novel, context-specific inhibitors of difficult targets, such as MYC and STAT3.
109 tcomes included item difficulty (how easy or difficult the question was), item discrimination (how we
110 arly in illness, making a clinical diagnosis difficult; therefore, laboratory testing is needed to co
111 ccessful syntheses of eighty-eight otherwise difficult to access compounds, in up to 99 % yields, inc
112  associated magnetic excitations have proven difficult to access with conventional techniques.
113 desirable for a variety of applications, but difficult to access with modern C-C bond-forming reactio
114 ereoselective Baeyer-Villiger oxidations are difficult to achieve by classical chemical means, partic
115 r the precise synaptic localization has been difficult to achieve due to the lack of adequate optical
116 zation of individual boundaries is vital yet difficult to achieve.
117 n-containing oxiranes can be troublesome and difficult to achieve.
118 societies for which reliable age records are difficult to acquire.
119  to the activity of these genes has remained difficult to address, due in part to unique challenges r
120 trition and resource costs of defence may be difficult to afford.
121 espond to complex signal combinations remain difficult to analyze and model.
122 poiesis, a developmental stage that has been difficult to analyze to date.
123          However, daily blood product use is difficult to anticipate.
124 abases and have different formats, making it difficult to apply LD score regression to estimate genet
125 environmental controls on high Rs values are difficult to ascertain due to limited field data.
126  neocortex in human evolution, it has proven difficult to ascertain whether this extent of prefrontal
127 e rate and drivers of population decline are difficult to assess accurately: species' surveys are typ
128 e, atmospheric and marine records, making it difficult to assess relationships between Antarctic ice-
129 variable over time and space, which makes it difficult to assess the average agronomic and economic i
130          Despite their importance, it can be difficult to assess the effects of floods on streamwater
131 ed by peripheral T-cell expansion, making it difficult to assess the role of thymic failure in human
132 e recurrence rates when melanoma margins are difficult to assess, and recurrence rates are high with
133 data that have proved to be less relevant or difficult to capture.
134 ansition, although these changes have proved difficult to characterize at a global scale.
135 and speciation of the halamines in water are difficult to characterize experimentally.
136 inition transient species, and therefore are difficult to characterize using current experimental tec
137 wever, the nature of this state has remained difficult to characterize.
138                               However, it is difficult to check for any bias in the peer-review proce
139          Few clades of plants have proven as difficult to classify as cacti.
140                     Since it has been rather difficult to compare detection limits across MPI publica
141  lacks a standardized methodology, making it difficult to compare published results.
142 ding to the generation of datasets which are difficult to compare.
143 up next to the protein-solvent interface are difficult to compensate by interactions with the protein
144 s in sample preparation and analysis make it difficult to confidently assign these numbers, limiting
145 versification shifts occur after WGDs, it is difficult to consider diversification and duplication to
146 e curvatures present in cells yet previously difficult to construct in vitro.
147 tively block FVIII activity, making bleeding difficult to control and prevent.
148 se nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple alle
149 s a complex biological process that has been difficult to delineate in human colorectal cancer (CRC)
150 te enzymes that alter PIP2 levels, making it difficult to delineate time- or region-specific roles of
151 molecules, and even nanoparticles, which are difficult to deploy in harsh reservoir conditions and wh
152 t solutions are costly, not versatile or are difficult to deploy.
153                    Complex DNA sequences are difficult to detect and profile, but are important contr
154 rall enthalpy of the protein, thus making it difficult to detect experimentally.
155  suggesting that microbubble echoes would be difficult to detect in such regions.
156 ltiple comparisons, wherein true signals are difficult to detect on the background of all association
157 especially in high-dimensional space, can be difficult to detect.
158 vely between individuals, but it can be very difficult to determine the sources of this heterogeneity
159 e-dimensional RNA structures are notoriously difficult to determine, and the link between secondary s
160  multicellular organisms, which remains very difficult to determine.
161 ug-resistant tuberculous meningitis (TBM) is difficult to diagnose and treat.
162 pical breakfast, lunch, and dinner meals are difficult to distinguish because skipping meals and snac
163               Because EVD and malaria can be difficult to distinguish clinically, and rapid testing w
164  have good thermoelectric performance but is difficult to dope experimentally.
165 o assess SDB or cognitive domains, making it difficult to draw conclusions on this association.
166  the rules governing such behavior have been difficult to elucidate [2].
167 ctional activity of this efflux pump is more difficult to elucidate, especially at the single-cell le
168 facilitate widespread adaptation may be very difficult to elucidate.
169  expense of modularity, making viral capsids difficult to engineer.
170 obesity and microbiome research have made it difficult to establish causality in this complex relatio
171                                       It was difficult to establish the order of transmetalation vs C
172 red salamander's exact distribution has been difficult to establish.
173 es, the functions of these enzymes are often difficult to establish.
174 uxes (e.g., crop uptake, leaching) have been difficult to estimate.
175  understood because it has been historically difficult to estimate.
176                      This makes it extremely difficult to evaluate the relative added value of each n
177 s often lowers the image contrast, making it difficult to examine cells and subcellular structures.
178   These patterns of atypical development are difficult to explain with existing models that emphasize
179 stant from the genes of origin, are far more difficult to find because millions of SNPs must currentl
180 (2+) NFL leading to adaptation that would be difficult to find by other means.
181 will form and what cargo it will contain are difficult to foresee.
182 tials and Frenkel defects are generally more difficult to form in Cr2AlC.
183  relatedness in plant communities, making it difficult to generalize responses of this major feature
184 at comprise 50% of the structure, making it difficult to generate an accurate homology model of the
185                             This has made it difficult to identify consistent host factors that expla
186  Pocillopora (Lamarck, 1816) are notoriously difficult to identify morphologically with considerable
187 dia, in North America or elsewhere, makes it difficult to identify the causes of such increases.
188 ch as bound biexcitons, are possible but are difficult to identify unambiguously using linear optical
189 epetitive regions of the genome and thus are difficult to identify with short reads.
190         However, because causal variants are difficult to identify, and cis-eQTLs occur frequently, i
191 the underlying neuronal correlates have been difficult to identify.
192 nd that global peptide-S/N relationships are difficult to identify.
193      However, current options are obtrusive, difficult to implement, and limited in their scope of ut
194  the complexity of the data, it is sometimes difficult to infer information about classes that are no
195                   Such diversity has made it difficult to infer the impact of these modulatory mechan
196 ts a few hundreds of milliseconds, making it difficult to infer underlying neural processes.
197                   However, these studies are difficult to interpret as they include migrants of vario
198                               However, it is difficult to interpret the results at the early stages o
199 ed to use and create visualizations that are difficult to interpret.
200 ractions and simulating the effects that are difficult to investigate experimentally.
201 parate from other individuals and objects is difficult to investigate in non-human animals.
202 transiently occurring intermediates that are difficult to isolate and characterize.
203                                This makes it difficult to isolate effects such as the role of Coulomb
204 evere periodontal conditions tend to be more difficult to manage conservatively and reliably.
205 ubled haploid systems are rare in nature and difficult to manage in breeding programmes.
206 hronic non-specific respiratory symptoms are difficult to manage.
207 e gender earnings gap, but these factors are difficult to measure.
208                          This requirement is difficult to meet in settings with sensitive data, which
209 h as carbon or gold/platinum, are costly and difficult to microfabricate.
210 ization processes are often rapid, it can be difficult to monitor their growth mechanisms.
211 motion of a room-temperature object and thus difficult to observe.
212 ecovery process at the atomic-scale has been difficult to observe.
213 ctions, yet such information is surprisingly difficult to obtain at the molecular level.
214  of enantiomerically pure compounds that are difficult to obtain by other asymmetric procedures.
215 ition of two high-resolution views otherwise difficult to obtain due to steric constraints at high nu
216 ptides and N-glycoproteins that are hitherto difficult to obtain for structural and functional studie
217           However, such information has been difficult to obtain for these two countries, as fast-pac
218 arget space within the host, which are often difficult to obtain from human subjects.
219 eories require experimental support which is difficult to obtain from the living eye.
220                               However, it is difficult to obtain quantitative data from microscopy an
221  materials and structures that are otherwise difficult to obtain, studies of the functions and proper
222 nd produce hybrids that, otherwise, would be difficult to obtain.
223 ause experiments with regular-sized pigs are difficult to perform.
224 omplex network of pathways exists, making it difficult to predict the effect of selected miRNAs on ag
225 o decadal changes in fire frequency makes it difficult to predict the effects of altered fire regimes
226                               However, it is difficult to predict their properties based on macroscop
227 erably between systems and have proven to be difficult to predict, spurring the need for new tools to
228 J) ankylosis is a refractory disease that is difficult to predictably treat.
229 on-noble metal nanoparticles are notoriously difficult to prepare and stabilize with appropriate disp
230 the other hand, alpha-sulfinyl chlorides are difficult to prepare with high levels of enantiopurity a
231 most available pharmaceuticals, but they are difficult to produce recombinantly, like many other aggr
232 tic structure of SN-38, it is typically very difficult to produce sub-100nm, SN-38-encapsulated nanop
233             Mantle carbon concentrations are difficult to quantify because most magmas are strongly d
234 omolar to millimolar dissociation constants) difficult to quantify under biologically relevant condit
235 linear increase in heat-related morbidity is difficult to quantify, hindering the attribution of dire
236 tion that would be otherwise easy to miss or difficult to quantify.
237 predictions produced by the various tools is difficult to quantify.
238 anscription of any given gene makes it often difficult to quickly identify the biological relevant tr
239 as microbes, central metabolism is extremely difficult to rationally engineer.
240 ses when a saved seed is allocated to a node difficult to reach via diffusion.
241 esize nanostructure assemblies that would be difficult to realize any other way and that could ultima
242                        Thus far, it has been difficult to recapitulate the features of germinative LE
243 icular, many crop species such as cotton are difficult to regenerate.
244 e fear to nonfearful fear stimuli, making it difficult to regulate anxiety.
245 l and evolutionary analysis results that are difficult to relate to one another.
246 lection are strongly interactive: it is more difficult to repeat a response in the context of a chang
247 uch as gliosis and fibrosis also can make it difficult to replenish and regenerate neurons.
248  associated with biofilm formation are often difficult to resolve without extended courses of antibio
249 s at the root of the animal tree have proven difficult to resolve, with the current debate focusing o
250  typically involves undefined components and difficult to scale 2D culture formats.
251                               However, it is difficult to scale down the size of these instruments du
252 d tedious routes that employ toxic and often difficult to scale pyrophoric reagents.
253                     However, it is currently difficult to select new biomarkers mainly due to limited
254 eterminant of T cell efficacy, it has proven difficult to selectively induce T cells of high function
255 ness and higher brain function, but has been difficult to selectively manipulate owing to cellular he
256 ti-epileptic drugs on individual neurons are difficult to separate from their network-level actions.
257 n species with female heterogamety (ZW), are difficult to sequence and assemble.
258 isomerism, and the cis isomers are much more difficult to stabilize than the trans forms.
259 d in the literature are highly disparate and difficult to structure, a new format of organizing, visu
260 well as liver-restricted disorders which are difficult to study by germline manipulation.
261 ther protein/small molecule systems that are difficult to study by traditional means.
262              The uncoating reaction has been difficult to study due to the rapid release of the genom
263                   Such transient species are difficult to study experimentally, but it has proven val
264 gnol oxidation and lignin polymerization are difficult to study in intact trees.
265 al role of these intracellular hydrogels are difficult to study, primarily due to technical challenge
266 ne resistance making functional consequences difficult to study.
267 ealth, reduced calorie diets are notoriously difficult to sustain.
268  all other protein-protein interactions, are difficult to target by small molecules.
269                     Because at present it is difficult to tell where sign stops and gesture begins, w
270                     While this prediction is difficult to test in epidemiological data on Caesarean s
271 n of antibodies can occur in infants but are difficult to track.
272 nt include host range specificity, making it difficult to translate from animal models to humans.
273 erile pustules, erosions, and crusts, EPD is difficult to treat and heals slowly.
274  Temporal lobe epilepsy is common and can be difficult to treat effectively.
275                         MRSA is particularly difficult to treat when it invades host cells and surviv
276  lesions, such as severely calcified, remain difficult to treat with DCB alone.
277          The resulting hyperglycemia is very difficult to treat, and patients are at risk for early m
278 plant severe renal insufficiency remain more difficult to treat, due to mechanisms of drug metabolism
279 rolonged excruciating pain, which has proven difficult to treat.
280 complex reaction with membranes, it has been difficult to uncover the molecular process that underlie
281 ere perceived as challenging to communicate, difficult to understand, unrealistic in terms of timelin
282                 The high error rates make it difficult to use this data alone, particularly with high
283 generated by flow cytometry usually makes it difficult to visualize.
284 n by the lack of functional annotations from difficult-to-characterize or rare cell populations.
285 cate that too long treatment times can cause difficult-to-handle modifications to the cellular redox
286    Pustular skin disorders are a category of difficult-to-treat and potentially life-threatening cond
287 ed high morbidity in patients with severe or difficult-to-treat asthma despite standard-of-care treat
288 ity, and severity in patients with severe or difficult-to-treat asthma.
289 e to Pseudomonas aeruginosa, an archetype of difficult-to-treat infection.
290 ides a foundation for future studies in this difficult-to-treat patient population.
291  the disease, compared with placebo, in this difficult-to-treat population.
292 , diagnosis, and therapeutic intervention in difficult-to-treat subjects.
293 re accurately than unfamiliar ones and under difficult viewing conditions when unfamiliar face recogn
294 -related processing while humans performed a difficult visual discrimination task.
295 s classification into simple, prolonged, and difficult weaning ignored weaning failure and presuppose
296 onal disorder of identical nanostructures is difficult, which in turn has limited experimental verifi
297 itis is under-recognized, since diagnosis is difficult with concomitant central nervous system (CNS)
298 ion permeability coefficients (Pd) of NPs is difficult with in vivo models.
299 rning protein-ligand interactions has proven difficult, with determination of entropic contributions
300  to alter their function or specificity is a difficult yet appealing challenge.

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