全文获取类型
收费全文 | 731篇 |
免费 | 38篇 |
出版年
2023年 | 4篇 |
2022年 | 8篇 |
2021年 | 17篇 |
2020年 | 7篇 |
2019年 | 15篇 |
2018年 | 23篇 |
2017年 | 16篇 |
2016年 | 37篇 |
2015年 | 39篇 |
2014年 | 45篇 |
2013年 | 45篇 |
2012年 | 49篇 |
2011年 | 59篇 |
2010年 | 39篇 |
2009年 | 32篇 |
2008年 | 65篇 |
2007年 | 49篇 |
2006年 | 45篇 |
2005年 | 36篇 |
2004年 | 39篇 |
2003年 | 25篇 |
2002年 | 34篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1983年 | 2篇 |
排序方式: 共有769条查询结果,搜索用时 437 毫秒
81.
Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin 总被引:2,自引:0,他引:2
Tanaka A Cleland MM Xu S Narendra DP Suen DF Karbowski M Youle RJ 《The Journal of cell biology》2010,191(7):1367-1380
Damage to mitochondria can lead to the depolarization of the inner mitochondrial membrane, thereby sensitizing impaired mitochondria for selective elimination by autophagy. However, fusion of uncoupled mitochondria with polarized mitochondria can compensate for damage, reverse membrane depolarization, and obviate mitophagy. Parkin, an E3 ubiquitin ligase that is mutated in monogenic forms of Parkinson's disease, was recently found to induce selective autophagy of damaged mitochondria. Here we show that ubiquitination of mitofusins Mfn1 and Mfn2, large GTPases that mediate mitochondrial fusion, is induced by Parkin upon membrane depolarization and leads to their degradation in a proteasome- and p97-dependent manner. p97, a AAA+ ATPase, accumulates on mitochondria upon uncoupling of Parkin-expressing cells, and both p97 and proteasome activity are required for Parkin-mediated mitophagy. After mitochondrial fission upon depolarization, Parkin prevents or delays refusion of mitochondria, likely by the elimination of mitofusins. Inhibition of Drp1-mediated mitochondrial fission, the proteasome, or p97 prevents Parkin-induced mitophagy. 相似文献
82.
Marek Lisowski Łukasz Jaremko Mariusz Jaremko Adam Mazur Rafał Latajka Maciej Makowski 《Biopolymers》2010,93(12):1055-1064
Conformations of two pairs of dehydropeptides with the opposite configuration of the ΔPhe residue, Boc‐Gly‐ΔZPhe‐Gly‐Phe‐OMe ( Z‐ OMe ), Boc‐Gly‐ΔEPhe‐Gly‐Phe‐OMe ( E‐ OMe ), Boc‐Gly‐ΔZPhe‐Gly‐Phe‐p‐NA ( Z‐p‐ NA ), and Boc‐Gly‐ΔEPhe‐Gly‐Phe‐p‐NA ( E‐p‐ NA ) were compared on the basis of CD and NMR studies in MeOH, trifluoroethanol (TFE), MeCN, chloroform, and dimethylsulfoxide (DMSO). The CD results were used as the additional input data for the NMR‐based determination of the detailed solution conformations of the peptides. It was found that E‐ OMe is unordered and Z‐ OMe , Z‐p‐ NA , and E‐p‐ NA adopt the β‐turn conformation. There are two overlapping β‐turns in each of those peptides: type II and type III′ in Z‐ OMe and Z‐p‐ NA , and two type III in E‐p‐ NA . The ordered structure‐inducing properties of ΔZPhe and ΔEPhe in the peptides studied depend on the C‐terminal blocking group. In methyl esters, the ΔZPhe residue is a strong inducer of ordered conformations whereas the ΔEPhe one has no such properties. In p‐nitroanilides, both isomers of ΔPhe cause the peptides to adopt ordered structures to a similar extent. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 1055–1064, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com 相似文献
83.
Ziolkowski W Szkatula M Nurczyk A Wakabayashi T Kaczor JJ Olek RA Knap N Antosiewicz J Wieckowski MR Wozniak M 《FEBS letters》2010,584(22):4606-4610
There is growing evidence of mitochondrial membrane raft-like microdomains that are involved in the apoptotic pathway. The aim of this study was to investigate the effect of methyl-beta-cyclodextrin (MβCD), being a well-known lipid microdomain disrupting agent and cholesterol chelator, on the structure and bioenergetics of rat liver mitochondria (RLM). We observed that MβCD decreases the function of RLM, induces changes in the mitochondrial configuration state and decreases the calcium chloride-induced swelling. These data suggest that disruption of mitochondrial raft-like microdomains by cholesterol efflux on one hand impairs mitochondrial bioenergetics, but on the other hand it protects the mitochondria from swelling. 相似文献
84.
Foltyn W Kos-Kudła B Siemińska L Zemczak A Strzelczyk J Marek B Kajdaniuk D Nowak M Borowska M Jurecka-Lubienicka B 《Endokrynologia Polska》2006,57(2):160-165
Neuroendocrine tumors are frequently associated with other primary malignancies. Plasmablastic lymphoma is a rare, aggressive neoplasm, derived from large B-cell, associated with human immunodeficiency virus infection. Plasmablastic lymphoma cells share many cytomorphologic and immunophenotypic features with plasmablastic cells, causing some diagnostic problems. We present a unique case of coexisting two very uncommon neoplasms: plasmablastic lymphoma and neuroendocrine carcinoma in 54-years-old men. This is the first report of caecum localization of plasmablastic lymphoma. Presented case images diagnostic problems in rare neoplasms. 相似文献
85.
86.
Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Szabadkai G Bianchi K Várnai P De Stefani D Wieckowski MR Cavagna D Nagy AI Balla T Rizzuto R 《The Journal of cell biology》2006,175(6):901-911
The voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane mediates metabolic flow, Ca(2+), and cell death signaling between the endoplasmic reticulum (ER) and mitochondrial networks. We demonstrate that VDAC1 is physically linked to the endoplasmic reticulum Ca(2+)-release channel inositol 1,4,5-trisphosphate receptor (IP(3)R) through the molecular chaperone glucose-regulated protein 75 (grp75). Functional interaction between the channels was shown by the recombinant expression of the ligand-binding domain of the IP(3)R on the ER or mitochondrial surface, which directly enhanced Ca(2+) accumulation in mitochondria. Knockdown of grp75 abolished the stimulatory effect, highlighting chaperone-mediated conformational coupling between the IP(3)R and the mitochondrial Ca(2+) uptake machinery. Because organelle Ca(2+) homeostasis influences fundamentally cellular functions and death signaling, the central location of grp75 may represent an important control point of cell fate and pathogenesis. 相似文献
87.
Brain-derived heat shock protein 70-peptide complexes induce NK cell-dependent tolerance to experimental autoimmune encephalomyelitis 总被引:1,自引:0,他引:1
Galazka G Stasiolek M Walczak A Jurewicz A Zylicz A Brosnan CF Raine CS Selmaj KW 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(3):1588-1599
Heat shock proteins (Hsp) are markedly up-regulated at sites of inflammation during autoimmune diseases like experimental autoimmune encephalomyelitis (EAE). In this study, we show that Hsp70-peptide complexes (pc) isolated from brains of mice with EAE prevented the development of EAE clinically and pathologically when administered before proteolipid protein 139-151 (PLP139-151) immunization. In contrast, pure Hsp70 or Hsp70-pc derived from brains of healthy mice or other inflamed tissue did not modulate the expression of EAE. In animals in which EAE had been suppressed by Hsp70-pc, lymphocytes showed increased cell death in response to PLP139-151 that correlated with elevated IFN-gamma and NO production. Coculture of spleen cells from Hsp70-pc immunized mice with spleen cells from untreated EAE mice, in addition to depletion experiments, showed that NK cells reduced reactivity to PLP139-151. Transfer of NK cells from Hsp70-pc-immunized mice to recipients sensitized for EAE abolished disease development. Thus, we propose that Hsp70 demonstrate the ability to bind to peptides generated during brain inflammation and to induce a regulatory NK cell population that is capable of preventing subsequent autoimmunization for EAE. 相似文献
88.
89.
90.
Staphylokinase is a 135 amino acid protein produced by certain strains of Staphylococcus aureus. It belongs to fibrin-specific plasminogen activator. Staphylokinase converts plasminogen--the inactive proenzyme--to the plasmin, which dissolves the fibrin of a blood clots. This review will focus on the biochemical and thrombolytic properties of staphylokinase and its derivatives, which would make use of treatment in acute myocardial infarction and other cardiovascular diseases. 相似文献