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排序方式: 共有318条查询结果,搜索用时 15 毫秒
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313.
Lihua He Andrew S. Kennedy Scott Houck Andrei Aleksandrov Nancy L. Quinney Alexandra Cyr-Scully Deborah M. Cholon Martina Gentzsch Scott H. Randell Hong Yu Ren Douglas M. Cyr 《Molecular biology of the cell》2021,32(7):538
The transmembrane Hsp40 DNAJB12 and cytosolic Hsp70 cooperate on the endoplasmic reticulum’s (ER) cytoplasmic face to facilitate the triage of nascent polytopic membrane proteins for folding versus degradation. N1303K is a common mutation that causes misfolding of the ion channel CFTR, but unlike F508del-CFTR, biogenic and functional defects in N1303K-CFTR are resistant to correction by folding modulators. N1303K is reported to arrest CFTR folding at a late stage after partial assembly of its N-terminal domains. N1303K-CFTR intermediates are clients of JB12-Hsp70 complexes, maintained in a detergent-soluble state, and have a relatively long 3-h half-life. ER-associated degradation (ERAD)-resistant pools of N1303K-CFTR are concentrated in ER tubules that associate with autophagy initiation sites containing WIPI1, FlP200, and LC3. Destabilization of N1303K-CFTR or depletion of JB12 prevents entry of N1303K-CFTR into the membranes of ER-connected phagophores and traffic to autolysosomes. In contrast, the stabilization of intermediates with the modulator VX-809 promotes the association of N1303K-CFTR with autophagy initiation machinery. N1303K-CFTR is excluded from the ER-exit sites, and its passage from the ER to autolysosomes does not require ER-phagy receptors. DNAJB12 operates in biosynthetically active ER microdomains to triage membrane protein intermediates in a conformation-specific manner for secretion versus degradation via ERAD or selective-ER-associated autophagy. 相似文献
314.
Jake W. Willows Morganne Robinson Zahra Alshahal Samantha K. Morrison Gargi Mishra Harrison Cyr Magdalena Blaszkiewicz Gilian Gunsch Sabrina DiPietro Emma Paradie Benjamin Tero Anne Harrington Larisa Ryzhova Lucy Liaw Peter C. Reifsnyder David E. Harrison Kristy L. Townsend 《Aging cell》2023,22(4):e13784
Neural communication between the brain and adipose tissues regulates energy expenditure and metabolism through modulation of adipose tissue functions. We have recently demonstrated that under pathophysiological conditions (obesity, diabetes, and aging), total subcutaneous white adipose tissue (scWAT) innervation is decreased (‘adipose neuropathy’). With advanced age in the C57BL/6J mouse, small fiber peripheral nerve endings in adipose tissue die back, resulting in reduced contact with adipose-resident blood vessels and other cells. This vascular neuropathy and parenchymal neuropathy together likely pose a physiological challenge for tissue function. In the current work, we used the genetically diverse HET3 mouse model to investigate the incidence of peripheral neuropathy and adipose tissue dysregulation across several ages in both male and female mice. We also investigated the anti-aging treatment rapamycin, an mTOR inhibitor, as a means to prevent or reduce adipose neuropathy. We found that HET3 mice displayed a reduced neuropathy phenotype compared to inbred C56BL/6 J mice, indicating genetic contributions to this aging phenotype. Compared to female HET3 mice, male HET3 mice had worse neuropathic phenotypes by 62 weeks of age. Female HET3 mice appeared to have increased protection from neuropathy until advanced age (126 weeks), after reproductive senescence. We found that rapamycin overall had little impact on neuropathy measures, and actually worsened adipose tissue inflammation and fibrosis. Despite its success as a longevity treatment in mice, higher doses and longer delivery paradigms for rapamycin may lead to a disconnect between life span and beneficial health outcomes. 相似文献
315.
Loren Cobb Louis Cyr Marcia K. Schmehl Harvey L. Bank 《In vitro cellular & developmental biology. Plant》1989,25(1):76-81
Summary This study reports the results of a critical comparison of five statistical methods for estimating the density of viable cells
in a limiting dilution assay (LDA). Artificial data were generated using Monte Carlo simulation. The performance of each statistical
method was examined with respect to the accuracy of its estimator and, most importantly, the accuracy of its associated estimated
standard error (SE). The regression method was found to perform at a level that is unacceptable for scientific research, due
primarily to gross underestimation of the SE. The maximum likelihood method exhibited the best overall performance. A corrected
version of Taswell's weighted-mean method, which provides the best performance among all noniterative methods examined, is
also presented. 相似文献
316.
Olfactory memory: the long and short of it 总被引:2,自引:2,他引:0
It has been proposed that memory for odors does not have a short-term (or
working) memory system. The distinction between short- and long- term
memory in other sensory modalities has been generally supported by three
main lines of evidence: capacity differences between the proposed systems,
evidence of differential coding, and differential memory losses in
neuropsychological patients. The present paper examines these issues in an
effort to establish a similar distinction for the memory of olfactory
stimuli. Each of these lines of evidence is examined in relation to the
literature on olfactory memory. Based on this examination, it seems that
there is at least preliminary support from each of these lines of evidence
to advocate a distinction between a long- and short-term memory for
olfactory stimuli. Emphasis is placed upon the qualitative similarity of
olfactory memory to other memory systems. This similarity is further
highlighted through an examination of the literature pertinent to serial
position effects in memory for olfactory stimuli.
相似文献
317.
Barry van Bergen Rona Strasser Normand Cyr John D. Sheppard Armando Jardim 《Biochimica et Biophysica Acta (BBA)/General Subjects》2006
An α,β-dicarbonyl reductase activity was purified from Saccharomyces cerevisiae and identified as the cytosolic enzyme d-Arabinose dehydrogenase (ARA1) by MALDI-TOF/TOF. Size exclusion chromatography analysis of recombinant Ara1p revealed that this protein formed a homodimer. Ara1p catalyzed the reduction of the reactive α,β-dicarbonyl compounds methylglyoxal, diacetyl, and pentanedione in a NADPH dependant manner. Ara1p had apparent Km values of ∼ 14 mM, 7 mM and 4 mM for methylglyoxal, diacetyl and pentanedione respectively, with corresponding turnover rates of 4.4, 6.9 and 5.9 s− 1 at pH 7.0. pH profiling showed that Ara1p had a pH optimum of 4.5 for the diacetyl reduction reaction. Ara1p also catalyzed the NADP+ dependant oxidation of acetoin; however this back reaction only occurred at alkaline pH values. That Ara1p was important for degradation of α,β-dicarbonyl substrates was further supported by the observation that ara1-Δ knockout yeast mutants exhibited a decreased growth rate phenotype in media containing diacetyl. 相似文献
318.