全文获取类型
收费全文 | 227篇 |
免费 | 9篇 |
国内免费 | 4篇 |
出版年
2023年 | 8篇 |
2022年 | 7篇 |
2021年 | 4篇 |
2020年 | 4篇 |
2019年 | 2篇 |
2018年 | 10篇 |
2017年 | 8篇 |
2016年 | 6篇 |
2015年 | 3篇 |
2014年 | 7篇 |
2013年 | 80篇 |
2012年 | 2篇 |
2011年 | 7篇 |
2010年 | 4篇 |
2009年 | 8篇 |
2008年 | 8篇 |
2007年 | 5篇 |
2006年 | 12篇 |
2005年 | 3篇 |
2004年 | 8篇 |
2003年 | 4篇 |
2002年 | 4篇 |
2001年 | 4篇 |
2000年 | 8篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1996年 | 4篇 |
1995年 | 1篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1977年 | 1篇 |
排序方式: 共有240条查询结果,搜索用时 31 毫秒
31.
William M. Holmes Courtney L. Klaips 《Critical reviews in biochemistry and molecular biology》2014,49(4):294-303
AbstractThe proper folding of proteins to their functional forms is essential to cellular homeostasis. Perhaps not surprisingly, cells have evolved multiple pathways, some overlapping and others complementary, to resolve mis-folded proteins when they arise, ranging from refolding through the action of molecular chaperones to elimination through regulated proteolytic mechanisms. These protein quality control pathways are sufficient, under normal conditions, to maintain a functioning proteome, but in response to diverse environmental, genetic and/or stochastic events, protein mis-folding exceeds the corrective capacity of these pathways, leading to the accumulation of aggregates and ultimately toxicity. Particularly devastating examples of these effects include certain neurodegenerative diseases, such as Huntington’s Disease, which are associated with the expansion of polyglutamine tracks in proteins. In these cases, protein mis-folding and aggregation are clear contributors to pathogenesis, but uncovering the precise mechanistic links between the two events remains an area of active research. Studies in the yeast Saccharomyces cerevisiae and other model systems have uncovered previously unanticipated complexity in aggregation pathways, the contributions of protein quality control processes to them and the cellular perturbations that result from them. Together these studies suggest that aggregate interactions and localization, rather than their size, are the crucial considerations in understanding the molecular basis of toxicity. 相似文献
32.
We investigated the evolutionary conservation of polyglutamine binding protein-1 (PQBP-1) among Vertebrata. PQBP-1s were highly conserved and shared the same domain features including a WW domain, a polar amino acid rich domain (PRD), a nuclear localization signal (NLS), and a C-terminal domain (CTD) among Eutheria, but not always among Vertebrata. PQBP-1s of Vertebrata contained a variable region in the middle portion corresponding to the position of PRD. The full form of PRD including both 7aa and DR/ER repeats was specific to Eutheria. PRD of non-eutherian Amniota was minimal. Amphibia had no PRD. The DR/ER repeat was solo in fishes. Agnatha PRD was also rich in polar amino acids, but contained no repetitive sequence. We investigated 3 polyQ-containing proteins known to interact with PQBP-1: BRN-2, Huntingtin, and ATAXIN-1, and showed a diverse nature of protein-protein interaction in Vertebrata. There appears to be no interaction between PQBP-1 and BRN-2, Huntingtin, or ATAXIN-1 in Amphibia, while the interaction between PQBP-1 and BRN-2 is expected to be conserved among Mammalia, and the interaction between PQBP-1 and Huntingtin or ATAXIN-1 depends on the lineage in Eutheria. 相似文献
33.
Simone S. Riedel Congcong Lu Hongbo M. Xie Kevin Nestler Marit W. Vermunt Alexandra Lenard Laura Bennett Nancy A. Speck Ichiro Hanamura Julie A. Lessard Gerd A. Blobel Benjamin A. Garcia Kathrin M. Bernt 《Molecular cell》2021,81(11):2332-2348.e9
- Download : Download high-res image (137KB)
- Download : Download full-size image
34.
《Structure (London, England : 1993)》2021,29(8):804-809.e5
- Download : Download high-res image (294KB)
- Download : Download full-size image
35.
Estella A. Newcombe Kiersten M. Ruff Ashish Sethi Angelique R. Ormsby Yasmin M. Ramdzan Archa Fox Anthony W. Purcell Paul R. Gooley Rohit V. Pappu Danny M. Hatters 《Journal of molecular biology》2018,430(10):1442-1458
Soluble huntingtin exon 1 (Httex1) with expanded polyglutamine (polyQ) engenders neurotoxicity in Huntington's disease. To uncover the physical basis of this toxicity, we performed structural studies of soluble Httex1 for wild-type and mutant polyQ lengths. Nuclear magnetic resonance experiments show evidence for conformational rigidity across the polyQ region. In contrast, hydrogen–deuterium exchange shows absence of backbone amide protection, suggesting negligible persistence of hydrogen bonds. The seemingly conflicting results are explained by all-atom simulations, which show that Httex1 adopts tadpole-like structures with a globular head encompassing the N-terminal amphipathic and polyQ regions and the tail encompassing the C-terminal proline-rich region. The surface area of the globular domain increases monotonically with polyQ length. This stimulates sharp increases in gain-of-function interactions in cells for expanded polyQ, and one of these interactions is with the stress-granule protein Fus. Our results highlight plausible connections between Httex1 structure and routes to neurotoxicity. 相似文献
36.
Genistein induces the metastasis suppressor kangai-1 which mediates its anti-invasive effects in TRAMP cancer cells 总被引:2,自引:0,他引:2
Previous studies demonstrated a direct correlation with loss of kangai-1 (KAI1), a metastasis suppressor, and poor prognosis in human prostate and other cancers. In this study, we have characterized the age-dependent downregulation of KAI1 in the TRAMP model which was reversed when mice were fed a genistein-enriched diet. We demonstrated here that doses of genistein (5 and 10 microM)--achievable by supplement intake--significantly induced the expression of KAI1, both at the mRNA and protein levels (up to 2.5-fold), and decreased the invasiveness of TRAMP-C2 cells >2.0-fold. We have pinpointed KAI1 as the invasion suppressor, since its knockdown by siRNA restored the invasive potential of genistein-treated TRAMP-C2 cells to control levels. This work provides the first evidence that genistein treatment may counteract KAI1 downregulation, which is observed in many cancer types and therefore, could be used in anti-metastatic therapies. 相似文献
37.
38.
39.
Matthias Lergenmüller Ulrich Klres Frieder W. Lichtenthaler 《Carbohydrate research》2009,344(16):2127-2136
Koenigs–Knorr-type glycosidations of peracylated 2Z-benzoyloxyimino-glycopyranosyl bromides invariably proceed with retention of the Z-geometry. Accordingly, the many β-d-hexosidulose oximes in literature which were prepared in this way and for which the oxime geometry has not been addressed explicitly, are the Z-oximes throughout. By contrast, oximation of β-d-hexopyranosid-2-uloses leads to mixtures of E and Z oximes readily separable and structurally verifiable by 1H and 13C NMR. Configurational assignments rested on comparative evaluation of NMR data of E and Z isomers, and, most notably on an X-ray structural analysis of the pivaloylated isopropyl 2E-benzoyloxyimino-2-deoxy-β-d-arabino-hexopyranoside revealing the unusual 1S51,4B conformation for the pyranoid ring. 相似文献
40.
Huang C Cheng H Hao S Zhou H Zhang X Gao J Sun QH Hu H Wang CC 《Journal of molecular biology》2006,364(3):323-336
alpha-Synuclein (AS) is a main component of Lewy bodies in midbrain dopamine neurons pathologically characteristic of Parkinson's disease. We show that heat shock protein (Hsp) 70 inhibits AS fibril formation via preventing the formation of prefibrillar AS (PreAS), binding with PreAS to impede nuclei formation, and binding with nuclei to retard fibril elongation. Also, Hsp70 suppresses the PreAS-induced permeabilization of vesicular membrane through interactions with PreAS. The substrate-binding domain alone is sufficient for Hsp70 to inhibit AS fibril formation. The binding of Hsp70 with PreAS only requires the substrate-binding subdomain, and the binding with AS nuclei requires the C-terminal lid subdomain as well. The results may form the molecular basis for elucidating the mechanism of AS fibril formation and the crucial roles of chaperones in protecting proteins from toxic conversion in many conformational diseases. 相似文献