全文获取类型
收费全文 | 565篇 |
免费 | 31篇 |
出版年
2023年 | 3篇 |
2022年 | 5篇 |
2021年 | 17篇 |
2020年 | 7篇 |
2019年 | 8篇 |
2018年 | 16篇 |
2017年 | 10篇 |
2016年 | 15篇 |
2015年 | 23篇 |
2014年 | 33篇 |
2013年 | 44篇 |
2012年 | 40篇 |
2011年 | 56篇 |
2010年 | 25篇 |
2009年 | 24篇 |
2008年 | 29篇 |
2007年 | 37篇 |
2006年 | 30篇 |
2005年 | 19篇 |
2004年 | 24篇 |
2003年 | 16篇 |
2002年 | 17篇 |
2001年 | 4篇 |
2000年 | 8篇 |
1999年 | 5篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1989年 | 3篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 9篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 4篇 |
1970年 | 1篇 |
1967年 | 2篇 |
排序方式: 共有596条查询结果,搜索用时 62 毫秒
41.
Derek P. Narendra Seok Min Jin Atsushi Tanaka Der-Fen Suen Clement A. Gautier Jie Shen Mark R. Cookson Richard J. Youle 《PLoS biology》2010,8(1)
Loss-of-function mutations in PINK1 and Parkin cause parkinsonism in humans and mitochondrial dysfunction in model organisms. Parkin is selectively recruited from the cytosol to damaged mitochondria to trigger their autophagy. How Parkin recognizes damaged mitochondria, however, is unknown. Here, we show that expression of PINK1 on individual mitochondria is regulated by voltage-dependent proteolysis to maintain low levels of PINK1 on healthy, polarized mitochondria, while facilitating the rapid accumulation of PINK1 on mitochondria that sustain damage. PINK1 accumulation on mitochondria is both necessary and sufficient for Parkin recruitment to mitochondria, and disease-causing mutations in PINK1 and Parkin disrupt Parkin recruitment and Parkin-induced mitophagy at distinct steps. These findings provide a biochemical explanation for the genetic epistasis between PINK1 and Parkin in Drosophila melanogaster. In addition, they support a novel model for the negative selection of damaged mitochondria, in which PINK1 signals mitochondrial dysfunction to Parkin, and Parkin promotes their elimination. 相似文献
42.
Holloway GP Thrush AB Heigenhauser GJ Tandon NN Dyck DJ Bonen A Spriet LL 《American journal of physiology. Endocrinology and metabolism》2007,292(6):E1782-E1789
A reduction in fatty acid oxidation has been associated with lipid accumulation and insulin resistance in the skeletal muscle of obese individuals. We examined whether this decrease in fatty acid oxidation was attributable to a reduction in muscle mitochondrial content and/or a dysfunction in fatty acid oxidation within mitochondria obtained from skeletal muscle of age-matched, lean [body mass index (BMI) = 23.3 +/- 0.7 kg/m2] and obese women (BMI = 37.6 +/- 2.2 kg/m2). The mitochondrial marker enzymes citrate synthase (-34%), beta-hydroxyacyl-CoA dehydrogenase (-17%), and cytochrome c oxidase (-32%) were reduced (P < 0.05) in obese participants, indicating that mitochondrial content was diminished. Obesity did not alter the ability of isolated mitochondria to oxidize palmitate; however, fatty acid oxidation was reduced at the whole muscle level by 28% (P < 0.05) in the obese. Mitochondrial fatty acid translocase (FAT/CD36) did not differ in lean and obese individuals, but mitochondrial FAT/CD36 was correlated with mitochondrial fatty acid oxidation (r = 0.67, P < 0.05). We conclude that the reduction in fatty acid oxidation in obese individuals is attributable to a decrease in mitochondrial content, not to an intrinsic defect in the mitochondria obtained from skeletal muscle of obese individuals. In addition, it appears that mitochondrial FAT/CD36 may be involved in regulating fatty acid oxidation in human skeletal muscle. 相似文献
43.
Thapa N Lee BH Kim IS 《The international journal of biochemistry & cell biology》2007,39(12):2183-2194
TGFBIp/βig-h3 protein is an extracellular matrix molecule initially cloned from human adenocarcinoma cells treated with TGF-β. Its precise function remains obscure but a number of studies have demonstrated it to be an intriguingly versatile molecule role in a wide range of physiological and pathological conditions. To date, the most extensively studied and reported action of TGFBIp/βig-h3 protein is in corneal dystrophy and several excellent reviews are available on this. Work from various laboratories on this molecule has compiled a tremendous amount of information over the past decade and a half. Here we review the current understanding on TGFBIp/βig-h3 protein and its functions in morphogenesis, extracellular matrix interactions, adhesion/migration, corneal dystrophy, tumorigenesis, angiogenesis, nephropathies, osteogenesis, wound healing and inflammation. 相似文献
44.
45.
46.
USP7 is a protein deubiquitinase with an essential role in development. Here, we provide evidence that USP7 regulates the activity of Polycomb repressive complex 1 (PRC1) in coordination with SCML2. There are six versions of PRC1 defined by the association of one of the PCGF homologues (PCGF1 to PCGF6) with the common catalytic subunit RING1B. First, we show that SCML2, a Polycomb group protein that associates with PRC1.2 (containing PCGF2/MEL18) and PRC1.4 (containing PCGF4/BMI1), modulates the localization of USP7 and bridges USP7 with PRC1.4, allowing for the stabilization of BMI1. Chromatin immunoprecipitation (ChIP) experiments demonstrate that USP7 is found at SCML2 and BMI1 target genes. Second, inhibition of USP7 leads to a reduction in the level of ubiquitinated histone H2A (H2Aub), the catalytic product of PRC1 and key for its repressive activity. USP7 regulates the posttranslational status of RING1B and BMI1, a specific component of PRC1.4. Thus, not only does USP7 stabilize PRC1 components, its catalytic activity is also necessary to maintain a functional PRC1, thereby ensuring appropriate levels of repressive H2Aub. 相似文献
47.
Auxin signaling and transport promote susceptibility to the root-infecting fungal pathogen Fusarium oxysporum in Arabidopsis 总被引:1,自引:0,他引:1
Kidd BN Kadoo NY Dombrecht B Tekeoglu M Gardiner DM Thatcher LF Aitken EA Schenk PM Manners JM Kazan K 《Molecular plant-microbe interactions : MPMI》2011,24(6):733-748
Fusarium oxysporum is a root-infecting fungal pathogen that causes wilt disease on a broad range of plant species, including the model plant Arabidopsis thaliana. Currently, very little is known about the molecular or physiological processes that are activated in the host during infection and the roles these processes play in resistance and susceptibility to F. oxysporum. In this study, we analyzed global gene expression profiles of F. oxysporum-infected Arabidopsis plants. Genes involved in jasmonate biosynthesis as well as jasmonate-dependent defense were coordinately induced by F. oxysporum. Similarly, tryptophan pathway genes, including those involved in both indole-glucosinolate and auxin biosynthesis, were upregulated in both the leaves and the roots of inoculated plants. Analysis of plants expressing the DR5:GUS construct suggested that root auxin homeostasis was altered during F. oxysporum infection. However, Arabidopsis mutants with altered auxin and tryptophan-derived metabolites such as indole-glucosinolates and camalexin did not show an altered resistance to this pathogen. In contrast, several auxin-signaling mutants were more resistant to F. oxysporum. Chemical or genetic alteration of polar auxin transport also conferred increased pathogen resistance. Our results suggest that, similarly to many other pathogenic and nonpathogenic or beneficial soil organisms, F. oxysporum requires components of auxin signaling and transport to colonize the plant more effectively. Potential mechanisms of auxin signaling and transport-mediated F. oxysporum susceptibility are discussed. 相似文献
48.
Narendra A Reid SF Greiner B Peters RA Hemmi JM Ribi WA Zeil J 《Proceedings. Biological sciences / The Royal Society》2011,278(1709):1141-1149
Animals are active at different times of the day and their activity schedules are shaped by competition, time-limited food resources and predators. Different temporal niches provide different light conditions, which affect the quality of visual information available to animals, in particular for navigation. We analysed caste-specific differences in compound eyes and ocelli in four congeneric sympatric species of Myrmecia ants, with emphasis on within-species adaptive flexibility and daily activity rhythms. Each caste has its own lifestyle: workers are exclusively pedestrian; alate females lead a brief life on the wing before becoming pedestrian; alate males lead a life exclusively on the wing. While workers of the four species range from diurnal, diurnal-crepuscular, crepuscular-nocturnal to nocturnal, the activity times of conspecific alates do not match in all cases. Even within a single species, we found eye area, facet numbers, facet sizes, rhabdom diameters and ocelli size to be tuned to the distinct temporal niche each caste occupies. We discuss these visual adaptations in relation to ambient light levels, visual tasks and mode of locomotion. 相似文献
49.
50.