全文获取类型
收费全文 | 5355篇 |
免费 | 503篇 |
国内免费 | 124篇 |
出版年
2024年 | 11篇 |
2023年 | 120篇 |
2022年 | 164篇 |
2021年 | 266篇 |
2020年 | 216篇 |
2019年 | 281篇 |
2018年 | 250篇 |
2017年 | 172篇 |
2016年 | 175篇 |
2015年 | 222篇 |
2014年 | 227篇 |
2013年 | 418篇 |
2012年 | 219篇 |
2011年 | 189篇 |
2010年 | 149篇 |
2009年 | 169篇 |
2008年 | 186篇 |
2007年 | 197篇 |
2006年 | 180篇 |
2005年 | 192篇 |
2004年 | 179篇 |
2003年 | 172篇 |
2002年 | 172篇 |
2001年 | 150篇 |
2000年 | 88篇 |
1999年 | 94篇 |
1998年 | 99篇 |
1997年 | 97篇 |
1996年 | 88篇 |
1995年 | 59篇 |
1994年 | 57篇 |
1993年 | 60篇 |
1992年 | 56篇 |
1991年 | 49篇 |
1990年 | 42篇 |
1989年 | 43篇 |
1988年 | 46篇 |
1987年 | 34篇 |
1986年 | 46篇 |
1985年 | 53篇 |
1984年 | 54篇 |
1983年 | 45篇 |
1982年 | 41篇 |
1981年 | 42篇 |
1980年 | 29篇 |
1979年 | 22篇 |
1978年 | 9篇 |
1977年 | 14篇 |
1974年 | 13篇 |
1973年 | 9篇 |
排序方式: 共有5982条查询结果,搜索用时 15 毫秒
991.
Strappazzon F Vietri-Rudan M Campello S Nazio F Florenzano F Fimia GM Piacentini M Levine B Cecconi F 《The EMBO journal》2011,30(7):1195-1208
BECLIN 1 is a central player in macroautophagy. AMBRA1, a BECLIN 1-interacting protein, positively regulates the BECLIN 1-dependent programme of autophagy. In this study, we show that AMBRA1 binds preferentially the mitochondrial pool of the antiapoptotic factor BCL-2, and that this interaction is disrupted following autophagy induction. Further, AMBRA1 can compete with both mitochondrial and endoplasmic reticulum-resident BCL-2 (mito-BCL-2 and ER-BCL-2, respectively) to bind BECLIN 1. Moreover, after autophagy induction, AMBRA1 is recruited to BECLIN 1. Altogether, these results indicate that, in normal conditions, a pool of AMBRA1 binds preferentially mito-BCL-2; after autophagy induction, AMBRA1 is released from BCL-2, consistent with its ability to promote BECLIN 1 activity. In addition, we found that the binding between AMBRA1 and mito-BCL-2 is reduced during apoptosis. Thus, a dynamic interaction exists between AMBRA1 and BCL-2 at the mitochondria that could regulate both BECLIN 1-dependent autophagy and apoptosis. 相似文献
992.
Pohjoismäki JL Goffart S 《BioEssays : news and reviews in molecular, cellular and developmental biology》2011,33(4):290-299
The organisation of mammalian mitochondrial DNA (mtDNA) is more complex than usually assumed. Despite often being depicted as a simple circle, the topology of mtDNA can vary from supercoiled monomeric circles over catenanes and oligomers to complex multimeric networks. Replication of mtDNA is also not clear cut. Two different mechanisms of replication have been found in cultured cells and in most tissues: a strand-asynchronous mode involving temporary RNA coverage of one strand, and a strand-coupled mode rather resembling conventional nuclear DNA replication. In addition, a recombination-initiated replication mechanism is likely to be associated with the multimeric mtDNA networks found in human heart. Although an insight into the general principles and key factors of mtDNA organisation and maintenance has been gained over the last few years, there are many open questions regarding replication initiation, termination and physiological factors determining mtDNA organisation and replication mode. However, common themes in mtDNA maintenance across eukaryotic kingdoms can provide valuable lessons for future work. 相似文献
993.
Ontogenetic changes in the location, size, density and morphology of chloride cells in the Nile tilapia Oreochromis niloticus adapted to fresh and brackish water are described using Na(+) /K(+) -ATPase immunohistochemistry, light microscopy (LM), scanning electron microscopy (SEM) and confocal scanning laser microscopy (CSLM). The pattern of chloride cell distribution changed during development under both treatments, with chloride cell density decreasing significantly from hatch to 7 days post-hatch, but appearing on the inner opercular area at 3 days post-hatch and increasing significantly thereafter (P < 0·05). Chloride cells were always denser in fresh- than in brackish-water larvae. In both treatments, chloride cells located on the outer operculum and tail showed a marked increase in size with age, but cells located on the abdominal epithelium of the yolk sac and the inner operculum showed a significant decrease in size (P < 0·05). Chloride cells from brackish-water adapted larvae from 1 day post-hatch onwards were always significantly larger (P < 0·05) than those from freshwater-adapted larvae. SEM revealed structural differences in chloride cell apical morphology according to environmental conditions. There appears to be clearly defined temporal staging of the appearance of adaptive mechanisms that confer an ability to cope with varying environmental conditions during early development. 相似文献
994.
995.
Hou Q Jin J Zhou H Novgorodov SA Bielawska A Szulc ZM Hannun YA Obeid LM Hsu YT 《Journal of lipid research》2011,52(2):278-288
C(6)-pyridinium (D-erythro-2-N-[6'-(1'-pyridinium)-hexanoyl]sphingosine bromide [LCL29]) is a cationic mitochondrion-targeting ceramide analog that promotes mitochondrial permeabilization and cancer cell death. In this study, we compared the biological effects of that compound with those of D-erythro-C(6)-ceramide, its non-mitochondrion-targeting analog. In MCF7 cells it was found that C(6)-pyridinium ceramide preferentially promoted autophagosome formation and retarded cell growth more extensively than its uncharged analog. This preferential inhibition of cell growth was also observed in breast epithelial cells and other breast cancer cells. In addition, this compound could promote Bax translocation to mitochondria. This redistribution of Bax in MCF7 cells could be blocked by the pan-caspase inhibitor zVAD-fmk but via a Bid-independent signaling pathway. Moreover, C(6)-pyridinium ceramide-induced translocation of Bax to mitochondria led to mitochondrial permeabilization and cell death. Overall, we show that mitochondrial targeting of C(6)-pyridinium ceramide significantly enhances cellular response to this compound. 相似文献
996.
Parkhomenko YM Kudryavtsev PA Pylypchuk SY Chekhivska LI Stepanenko SP Sergiichuk AA Bunik VI 《Journal of neurochemistry》2011,117(6):1055-1065
Thiamine-dependent changes in alcoholic brain were studied using a rat model. Brain thiamine and its mono- and diphosphates were not reduced after 20 weeks of alcohol exposure. However, alcoholism increased both synaptosomal thiamine uptake and thiamine diphosphate synthesis in brain, pointing to mechanisms preserving thiamine diphosphate in the alcoholic brain. In spite of the unchanged level of the coenzyme thiamine diphosphate, activities of the mitochondrial 2-oxoglutarate and pyruvate dehydrogenase complexes decreased in alcoholic brain. The inactivation of pyruvate dehydrogenase complex was caused by its increased phosphorylation. The inactivation of 2-oxoglutarate dehydrogenase complex (OGDHC) correlated with a decrease in free thiols resulting from an elevation of reactive oxygen species. Abstinence from alcohol following exposure to alcohol reactivated OGDHC along with restoration of the free thiol content. However, restoration of enzyme activity occurred before normalization of reactive oxygen species levels. Hence, the redox status of cellular thiols mediates the action of oxidative stress on OGDHC in alcoholic brain. As a result, upon chronic alcohol consumption, physiological mechanisms to counteract the thiamine deficiency and silence pyruvate dehydrogenase are activated in rat brain, whereas OGDHC is inactivated due to impaired antioxidant ability. 相似文献
997.
Wei T Miyazaki N Uehara-Ichiki T Hibino H Shimizu T Netsu O Kikuchi A Sasaya T Iwasaki K Omura T 《Journal of molecular biology》2011,410(3):436-446
Examination of cultured insect vector cells that had been infected with Rice gall dwarf virus (RGDV), using transmission electron microscopy and confocal microscopy, revealed the presence of clusters of virus-coated mitochondria around viroplasms in which replication and assembly of RGDV occurred, suggesting a role for mitochondria in supplying the energy required for viral morphogenetic processes. Electron tomography revealed that RGDV particles on the surface of mitochondria are arrayed in an orderly but loose manner, unlike tightly packaged particles in vesicular compartments, suggesting the presence of counterpart molecules on the surface of mitochondria. The viral particles in close proximity to mitochondria were aligned along intermediate filaments, which might serve as scaffolds for the anchorage of these particles. RGDV has a putative mitochondrion-targeting sequence on the outer surface of the outer-capsid protein P8. The arrangement of RGDV particles around mitochondria suggests that the region of the P8 protein containing the mitochondrion-targeting sequence might attach to a molecule like a receptor on the outer mitochondrial membrane. Our analysis demonstrates the three-dimensional arrangement and molecular basis for the mitochondrial proximity of RGDV particles during viral replication. 相似文献
998.
One of the most citated characteristics of eukaryotic cells are mitochondria and in the case of phototrophic cells, the plastids. These organelles are of eubacterial origin and contain a remnant genome. Here, we present hypotheses concerning the origin of the first mitochondrium-harboring cell and show the evolution of primary, secondary and tertiary plastids. Furthermore we discuss models explaining why plastids have to maintain their own genome. 相似文献
999.
Tamara Azarashvili Irina Odinokova Anush Bakunts Vadim Ternovsky Olga Krestinina Jaana Tyynelä Nils-Erik Leo Saris 《Cell calcium》2014
Phosphorylated and non-phosphorylated forms of the F0F1-ATPase subunit c from rat liver mitochondria (RLM) were purified and their effect on the opening of the permeability transition pore (mPTP) was investigated. Addition of dephosphorylated subunit c to RLM induced mitochondrial swelling, decreased the membrane potential and reduced the Ca2+ uptake capacity, which was prevented by cyclosporin A. The same effect was observed in the presence of storage subunit c purified from livers of sheep affected with ceroid lipofuscinosis. In black-lipid bilayer membranes subunit c increased the conductance due to formation of single channels with fast and slow kinetics. The dephosphorylated subunit c formed channels with slow kinetics, i.e. the open state being of significantly longer duration than in the case of channels formed by the phosphorylated form that had short life spans and fast kinetics. The channels formed were cation-selective more so with the phosphorylated form. Subunit c of rat liver mitochondria was able to bind Ca2+. Collectively, the data allowed us to suppose that subunit c F0F1-ATPase might be a structural/regulatory component of mPTP exerting its role in dependence on phosphorylation status. 相似文献
1000.
The interface between mitochondria and the endoplasmic reticulum is emerging as a crucial hub for calcium signalling, apoptosis, autophagy and lipid biosynthesis, with far reaching implications in cell life and death and in the regulation of mitochondrial and endoplasmic reticulum function. Here we review our current knowledge on the structural and functional aspects of this interorganellar juxtaposition. This article is part of a Special Issue entitled: Calcium Signaling In Health and Disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau. 相似文献