ライフサイエンスコーパス: ha(s|ve|d) prove(d|n) difficult

1 nd loading using microfabrication technology has proved difficult.

2 targeting of Ras proteins by small molecules has proved difficult.

3 ces during behaviorally-relevant motor tasks has proved difficult.

4 y, implementation of the IOM recommendations has proved difficult.

5 y for directing conservation investments but has proved difficult.

6 polyglutamine proteins in the brain and body has proved difficult.

7 at self-assemble into non-compact structures has proved difficult.

8 t quantitation of the rate of transfer often has proved difficult.

9 rare BRCA2 missense mutations on cancer risk has proved difficult.

10 pharmacological sensitivity in target organs has proved difficult.

11 key functional distinctions between species has proved difficult.

12 replication of initial association findings has proved difficult.

13 ive clinical therapy for Parkinson's disease has proved difficult.

14 the parameters that lead to immunodominance has proved difficult.

15 ver, assembling evidence for this hypothesis has proved difficult.

16 biomolecular signalling cues in such systems has proved difficult.

17 p(3) C-H bonds in C-C bond forming reactions has proved difficult.

18 t large spatial scales in natural landscapes has proven difficult.

19 he Co(dmgBF2)2L2 system, but its observation has proven difficult.

20 t identifying specific underlying mechanisms has proven difficult.

21 ncer but its effective therapeutic targeting has proven difficult.

22 targeting the resulting deregulated pathways has proven difficult.

23 complete eradication of established disease has proven difficult.

24 unds with high specificity among the kinases has proven difficult.

25 this mechanism for membrane-bound receptors has proven difficult.

26 g artificial DBDs, designing artificial TADs has proven difficult.

27 ,4-hydroxycarbonyls in OH + alkane reactions has proven difficult.

28 ibutions of ECM stiffness and dimensionality has proven difficult.

29 in-based concepts into novel polymer designs has proven difficult.

30 rved, but delineation of the PWS-IC in mouse has proven difficult.

31 er, yet the identification of relevant genes has proven difficult.

32 rammable shapes outside a liquid environment has proven difficult.

33 ers, but identifying the neurons responsible has proven difficult.

34 plementation of this gain-of-function system has proven difficult.

35 finding chemically defined, robust substrata has proven difficult.

36 identification of Ags that elicit these Abs has proven difficult.

37 fication of physiologically relevant ligands has proven difficult.

38 tion of genes that predispose to the illness has proven difficult.

39 ese actions in chemically identified neurons has proven difficult.

40 study from patients with autoimmune disease has proven difficult.

41 een numerically expanded by in vitro culture has proven difficult.

42 onmental factors in this burgeoning epidemic has proven difficult.

43 effective therapies to stimulate contraction has proven difficult.

44 ate, a state that is by definition inactive, has proven difficult.

45 ng the underlying reasons for this variation has proven difficult.

46 cytotoxic effect on slow-growing tumor cells has proven difficult.

47 mpact of drug candidates on human toxicology has proven difficult.

48 (WPV) cases since 1988, tackling the last 1% has proven difficult.

49 hematopoietic stem cells in irradiated mice has proven difficult.

50 f catalyzing efficient full-site integration has proven difficult.

51 ppropriate internal controls for such assays has proven difficult.

52 ar immune responses by vaccination in humans has proven difficult.

53 Directly relating these two roles has proven difficult.

54 chondrial DNA (mtDNA) within mammalian cells has proven difficult.

55 pact of DAT changes on drug taking behaviors has proven difficult.

56 ols to accurately capture splicing variation has proven difficult.

57 turbation of ROS at the organellar interface has proven difficult.

58 uptake by the liver in live model organisms has proven difficult.

59 t characterizing production by source sector has proven difficult.

60 that stimulates a tolerance-inducing pathway has proven difficult.

61 d assays, but moving RET into intact animals has proven difficult.

62 levels of voluntary drinking in these models has proven difficult.

63 g immunogens that recapitulate such epitopes has proven difficult.

64 dependent on infiltrating inflammatory cells has proven difficult.

65 ning of a polydisperse assembly of particles have proved difficult.

66 ind-wave coupling, but detailed observations have proved difficult.

67 nd producing paCOS with patterns of interest have proven difficult.

68 erance and determining its behavioral impact have proven difficult.

69 derpinnings and teasing apart its components have proven difficult.

70 Vaccine development has proved difficult and resistance has emerged for most

71 spersion of particles in polymeric materials has proven difficult and frequently results in phase sep

72 Demonstrating this potential, however, has proven difficult and is restricted to structurally s

73 table OPCs from human pluripotent stem cells has proven difficult and primary OPCs are not readily av

74 covery of hepatitis C virus (HCV), treatment has proven difficult and the regimen of pegylated interf

75 Describing this transition quantitatively has proved difficult, and one of the main unsolved probl

76 , or sensory neurons, throughout the cochlea has proven difficult, and no studies have been able to e

77 derlying such putatively multiquantal events has proven difficult at hair cell synapses, hindering co

78 linking quantum-enabled devices with cables has proved difficult because most cavity or circuit quan

79 h-temperature cuprate superconductors (HTSs) has proved difficult because of the presence of high-ang

80 eurochemical pathways that govern aggression has proven difficult because monoaminergic neurons also

81 c influence in amyotrophic lateral sclerosis has proven difficult because mSOD1 is ubiquitously expre

82 cytokine IL-10 at the level of the granuloma has proven difficult because of lesional heterogeneity a

83 hin the genetic code in untranslated regions has proven difficult because of the ambiguity of microRN

84 erapies to treat peripheral vascular disease has proven difficult because of the contribution of mult

85 However, studying astrocytes has proven difficult because of the lack of tools permit

86 he stabilization of these types of complexes has proven difficult because of the tendency to form oxo

87 This type of analysis has proven difficult because reconstitution approaches h

88 Probing for these intermediates has proven difficult because the concentrations of detec

89 Attaining a structure of Dda has proven difficult because the protein fails to readil

90 but molecularly distinct subgroups of cancer has proven difficult because their defining genetic alte

91 Past studies of this question have proven difficult because microstimulation interfere

92 Furthermore, cross-platform comparisons have proven difficult because reported concentrations ar

93 This question has proven difficult, because patterns of functional con

94 rrowing the bandgap of TiO(2) through doping have proven difficult, because of defect-induced charge

95 Genetic approaches to study this question have proven difficult, because of the redundancy of liga

96 dividual effector proteins in SCV biogenesis has proven difficult but several distinct themes are now

97 ing persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally

98 pluripotent cells to mature skeletal muscle have proved difficult challenges for regenerative biolog

99 ver, comparing results from such experiments has proved difficult due to influences from variations i

100 he structure of natively disordered peptides has proved difficult due to the lack of structural infor

101 s indirectly through spin relaxation effects has proven difficult due to competing relaxation mechani

102 Determining its biological function has proven difficult due to lack of knowledge regarding

103 However, developing this understanding has proven difficult due to rapid and uncontrolled cryst

104 elucidate the full-length structure of NEMO have proved difficult due to its apparent high conformat

105 r histologic location in normal mouse spleen have proven difficult due to both their paucity and low

106 an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of

107 al relevance of the hippocampal theta rhythm has proven difficult, due to a shortage of experiments t

108 water availability, predicting this response has proven difficult, especially in temperate regions th

109 the early diversification of animal lineages has proven difficult, even using genome-scale datasets.

110 But it has proved difficult for existing spectrographs to chara

111 after a conductive film is achieved, doping has proven difficult for further control of the optoelec

112 odels, such complex behavior-based screening has proven difficult for recovering genes in vertebrates

113 r several molecular motors, these approaches have proved difficult for membrane bound molecular motor

114 Interpreting the (18)O/(16)O variability has proved difficult, however, because oxygen isotopes i

115 It has proved difficult, however, to distinguish between th

116 Selection for host resistance has proven difficult, however, due to low heritability e

117 It has proven difficult, however, to determine the specific

118 onal magnetic resonance imaging (fMRI) alone has proven difficult, however.

119 This approach has proven difficult in neuroscience due to the marked d

120 alculated with the Nernst equation, but this has proven difficult in practice due to fluorescence que

121 le or transgenic manipulation of Ngf or Trka have proved difficult in addressing this question.

122 stablishing their phylogenetic relationships have proved difficult in some cases.

123 Resolving this question has proven difficult, in large part because of the sizea

124 plete with many orphans of unknown function, has proven difficult, in part because high-throughput sc

125 rrelates of effective CD8(+) T-cell immunity has proven difficult; notably, comprehensive analyses ha

126 this structure-stability relation, however, has proved difficult owing to a sampling bias (data avai

127 phases exhibiting varying degrees of order, has proved difficult owing to the contribution of electr

128 t obtaining potent small-molecule inhibitors has proved difficult owing to the necessity of targeting

129 of anatomically modern Homo sapiens occurred has proved difficult, particularly because Africa lacked

130 ble individual trait of general intelligence has proved difficult, particularly in the rapidly develo

131 ippi River basin and tracking their invasion has proven difficult, particularly where abundance is lo

132 ochemical approaches addressing the dynamics have proven difficult, particularly in complicated multi

133 tial hypertension and other complex diseases has proved difficult, partly because of genetic heteroge

134 tation rates on bedrock river incision rates has proved difficult, partly because river incision rate

135 ling the neurological aspect of this disease has proven difficult since murine models fail to mirror

136 However, achieving this goal has proven difficult since NUE is a complex trait encomp

137 terization of these oligomeric intermediates has proven difficult, sparking controversy over their bi

138 ween microstructural details and performance have proven difficult tasks.

139 ground states, this electronic configuration has proved difficult to achieve in a molecular species.

140 terials, control over 'multistate' materials has proved difficult to achieve.

141 res in the target materials), something that has proved difficult to achieve.

142 However, high-efficiency depletion has proved difficult to achieve.

143 capping and length regulation, its function has proved difficult to analyze.

144 rmediate populations have been described, it has proved difficult to characterize the rare, asynchron

145 Although it has proved difficult to combat this disease, one strateg

146 ft towards culture-independent approaches it has proved difficult to derive useful information about

147 lthough the precise function of this element has proved difficult to determine.

148 e nucleotide polymorphism (SNP) variants, it has proved difficult to discover independent causal vari

149 ar mechanism of the type IV secretion system has proved difficult to dissect in the absence of struct

150 rA dynamics with regular plasmid positioning has proved difficult to dissect.

151 It has proved difficult to distinguish between air-to-sea c

152 vergence and admixture from genomic data, it has proved difficult to distinguish recent admixture fro

153 This claim has proved difficult to establish due to the absence of

154 However, this hypothesis has proved difficult to examine directly because atomic

155 In particular, it has proved difficult to exploit the information containe

156 Furthermore, it has proved difficult to find a clear correlation between

157 In many such cases, it has proved difficult to identify a genetic cause.

158 e to model complexity, the origin of the NPL has proved difficult to identify.

159 tial for osteocyte survival and function but has proved difficult to measure.

160 number of sexual partners over time, but it has proved difficult to obtain parameter estimates relat

161 ctural information for the eukaryotic enzyme has proved difficult to obtain.

162 ly simplified microscopic endoparasites that has proved difficult to place phylogenetically.

163 such as the fractional quantum Hall effect, has proved difficult to probe spectroscopically.

164 It has proved difficult to quantify premature mortality rel

165 actory neurobiological understanding of itch has proved difficult to reach.

166 This immune response has proved difficult to restore by therapeutic vaccinati

167 However, it has proved difficult to separate the role of raised chlo

168 stable, both genetically and physically, but has proved difficult to study.

169 e to cancer-causing mutations; however, this has proved difficult to test because the identity of mos

170 It has proved difficult to understand how these factors inf

171 However, it has proved difficult to visualize and genetically probe

172 However, it has proven difficult to accomplish this goal with peptid

173 However, it has proven difficult to accurately quantify evolutionary

174 However, it has proven difficult to achieve tailored long-range orde

175 However, wide metabolome coverage has proven difficult to achieve, mostly because of the d

176 and to further translational studies, but it has proven difficult to achieve.

177 rest, the role of SETDB1/ESET in development has proven difficult to address.

178 umstances, electrospray based aerosolization has proven difficult to apply for this purpose.

179 ive motor proteins such as kinesin-1, but it has proven difficult to apply these approaches to nonpro

180 sion of the neocortex in human evolution, it has proven difficult to ascertain whether this extent of

181 filin and inhibit its interaction with actin has proven difficult to ascertain.

182 ding of metal ions such as Pt(2+) and Pd(2+) has proven difficult to assess via UV-vis spectroscopy b

183 ty for AIDS vaccine development but one that has proven difficult to be achieved.

184 g past population history and health, but it has proven difficult to characterize archaeologically.

185 ivity or thermodynamic stability of proteins has proven difficult to characterize.

186 ple chemical components of this envelope, it has proven difficult to combine its components into a co

187 erent complexity of discrete neural circuits has proven difficult to decipher, many parallel methodol

188 elopment exhibits broad political appeal but has proven difficult to define in precise terms.

189 However, it has proven difficult to describe native microstates beca

190 ll mice die during embryonic development, it has proven difficult to determine the functions of Notch

191 initiation and progression of this syndrome has proven difficult to determine.

192 es of interaction have been proposed, but it has proven difficult to discriminate which ones are impl

193 o occur in retinotopic visual cortex, but it has proven difficult to distinguish the contributions of

194 ay a role in this response to injury, but it has proven difficult to distinguish whether it is stimul

195 feration of CAR-redirected T lymphocytes, it has proven difficult to draw definitive conclusions abou

196 Nevertheless, the ICL repair process has proven difficult to elucidate.

197 a small increase in the risk of AML, but it has proven difficult to establish whether AML is actuall

198 The prevalence of mitochondrial disease has proven difficult to establish, predominantly as a re

199 le of cortical layers within auditory cortex has proven difficult to establish.

200 Therefore, it has proven difficult to extrapolate experimental results

201 replicate efficiently in cultured cells, it has proven difficult to generate efficiently replicating

202 Because of its size, PC1 has proven difficult to handle biochemically, and struct

203 However, it has proven difficult to identify and characterize the ga

204 that multiple variants are involved, but it has proven difficult to identify individual risk variant

205 However, it has proven difficult to identify the reactive sites in n

206 This strategy has proven difficult to implement therapeutically, and h

207 ses have had a distinguished history, but it has proven difficult to improve their predictive power s

208 on and survival of the organism; however, it has proven difficult to infer the relative importance of

209 gration in initiation of T(CD8(+)) responses has proven difficult to interpret because injected virus

210 Despite this, synaptic biology has proven difficult to interrogate directly in situ due

211 emories are encoded by specific circuits, it has proven difficult to localize learning within a corti

212 This hairpin sequence has proven difficult to manipulate in the context of the

213 have received considerable attention, yet it has proven difficult to measure monolayer and interfacia

214 he needs, the conventional microscope design has proven difficult to miniaturize.

215 ructure for unliganded TLR3-ECD; however, it has proven difficult to obtain a crystal structure of TL

216 e found computationally in many exons but it has proven difficult to predict whether a given mutation

217 species and environments, but this variation has proven difficult to predict, presenting a major chal

218 Implicated in a range of reactions, it has proven difficult to quantify its spatial distributio

219 orward to observe using fluorescent tracers, has proven difficult to quantify.

220 But, it has proven difficult to realize spintronic circuits with

221 cial stadial events, the magnitude of shifts has proven difficult to reconstruct, in part because of

222 es in ubiquitin-mediated protein degradation has proven difficult to resolve due to their overlapping

223 tightly linked to available moisture, yet it has proven difficult to resolve what aspects of climate

224 o the rapid radiation, the Pecoran phylogeny has proven difficult to resolve, and 11 of the 15 possib

225 conservation in the presence of dissipation has proven difficult to resolve.

226 important determinant of T cell efficacy, it has proven difficult to selectively induce T cells of hi

227 Gossypium hirsutum has proven difficult to sequence owing to its complex al

228 It has proven difficult to show direct actions of UVA as a

229 cii cannot be reliably cultured in vitro, it has proven difficult to study and gaps in our understand

230 relevant or particularly salient stimuli, it has proven difficult to study interactions between top-d

231 inically relevant G protein-coupled receptor has proven difficult to study, as it must form an obliga

232 As Ras has proven difficult to target therapeutically, we searc

233 at the brain displays attractor dynamics, it has proven difficult to test experimentally whether any

234 However, it has proven difficult to test this hypothesis, and a dire

235 ifests as prolonged excruciating pain, which has proven difficult to treat.

236 It has proven difficult to tune resonant transmission in di

237 ever, in almost all experimental systems, it has proven difficult to unravel the complex signaling pa

238 a wide range of biomedical applications, it has proven difficult to use them to generate high-qualit

239 ly exploited for prokaryotic genome analysis have proved difficult to apply to eukaryotes, however, a

240 icultural transition, although these changes have proved difficult to characterize at a global scale.

241 ts, but have been largely overlooked as they have proved difficult to culture in the laboratory.

242 n cognitive function in postmenopausal women have proved difficult to define.

243 accurate predictions and effective solutions have proved difficult to formulate.

244 iants involved in the pathogenesis of asthma have proved difficult to identify by candidate gene asso

245 e constituents in plants that promote health have proved difficult to identify with certainty.

246 cated in inflammation, such cells themselves have proved difficult to isolate and characterize.

247 lving spatially heterogeneous reactions that have proved difficult to resolve with existing technique

248 in the angiosperm branch of the Tree of Life have proved difficult to resolve.

249 nomena related to starch gelatinization that have proved difficult to study by other means.

250 rrelated spin systems, such as spin liquids, have proved difficult to study, in part because calculat

251 usive as the associated magnetic excitations have proven difficult to access with conventional techni

252 These are long-standing questions that have proven difficult to answer.

253 thetic supramolecular architectures in water have proven difficult to ascertain.

254 experiments exhibits unusual properties that have proven difficult to capture well by molecular model

255 uired to convert large RNAs into active RNPs have proven difficult to characterize fully.

256 These include environmental DNA samples that have proven difficult to clone and synthetic genes encod

257 ce of data for uncovering these subtypes but have proven difficult to compare, as two tumors rarely s

258 evant LAA-specific CD8(+) T-cell populations have proven difficult to define.

259 at utilize protein-carbohydrate interactions have proven difficult to design, primarily because the f

260 vo kinetics of these individual interactions have proven difficult to determine with precision since

261 However, cell active pan-Pim inhibitors have proven difficult to develop because Pim-2 has a low

262 However, many of these agonist molecules have proven difficult to develop clinically.

263 Antibodies specific to p53 protein isoforms have proven difficult to develop, thus researchers must

264 These 2 accounts have proven difficult to discriminate between.

265 However, these questions have proven difficult to dissect using molecular genetic

266 , the molecular pathways underlying feedback have proven difficult to elucidate using conventional ge

267 s in the liver, the site of HCV replication, have proven difficult to elucidate.

268 ssion would be ideal for in vivo imaging but have proven difficult to engineer.

269 Adult somatic tissues have proven difficult to expand in vitro, largely becaus

270 ists for decades, but until recently answers have proven difficult to find.

271 on, inheritance is complex, and risk alleles have proven difficult to identify.

272 To date, downstream targets of Hox genes have proven difficult to identify.

273 However, they have proven difficult to inhibit: very few good inhibito

274 ies on developmental differences and changes have proven difficult to integrate.

275 ions in highly repetitive regions of genomes have proven difficult to map since short reads of 50-100

276 combinations of strength and toughness, but have proven difficult to mimic synthetically.

277 common complications of cancer therapy that have proven difficult to model in mice.

278 ty acid on cholesterol-membrane interactions have proven difficult to monitor in real time in intact

279 neuronal activity, yet confirmative findings have proven difficult to obtain.

280 innings of this temperature-sensitive gating have proven difficult to parse.

281 nd catalytic effect of these electric fields have proven difficult to quantify with standard experime

282 cycle, rates of biological nitrogen fixation have proven difficult to quantify.

283 tes of disease detection in communities that have proven difficult to reach and to link to appropriat

284 t with liquid flows at these same latitudes, have proven difficult to reconcile.

285 ratus whose origins and evolutionary history have proven difficult to reconstruct.

286 relationships at the root of the animal tree have proven difficult to resolve, with the current debat

287 DNA-binding domains, including several that have proven difficult to study by other techniques.

288 specific details of how this process occurs have proven difficult to study, especially as Dsh appear

289 However, Ras proteins have proven difficult to target directly.

290 tify small-molecule probes for proteins that have proven difficult to target using high-throughput sc

291 However, these ideas have proven difficult to test.

292 However, rafts have proven difficult to visualize in living cells.

293 ods and also enables the study of cells that have proved difficult traditionally to transfect (e.g. t

294 from other cell types, a critical step which has proven difficult using surface-marker approaches.

295 equires accurate quantification of PD, which has proven difficult using transmission electron microsc

296 y of molecules to the central nervous system has proven difficult, we recently discovered that adeno-

297 ed domains of multimeric ectodomain proteins has proven difficult, we report a method to rapidly prod

298 tmospheric CO2 levels as a driver of the MPT has proven difficult with available observations.

299 hates under plausible early Earth conditions has proved difficult, with the incorporation of phosphor

300 terms governing protein-ligand interactions has proven difficult, with determination of entropic con