全文获取类型
收费全文 | 651篇 |
免费 | 48篇 |
专业分类
699篇 |
出版年
2022年 | 7篇 |
2021年 | 14篇 |
2020年 | 4篇 |
2019年 | 16篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 15篇 |
2015年 | 29篇 |
2014年 | 35篇 |
2013年 | 29篇 |
2012年 | 46篇 |
2011年 | 47篇 |
2010年 | 34篇 |
2009年 | 23篇 |
2008年 | 49篇 |
2007年 | 26篇 |
2006年 | 33篇 |
2005年 | 18篇 |
2004年 | 18篇 |
2003年 | 18篇 |
2002年 | 11篇 |
2001年 | 10篇 |
2000年 | 9篇 |
1999年 | 17篇 |
1998年 | 4篇 |
1997年 | 10篇 |
1996年 | 7篇 |
1995年 | 12篇 |
1994年 | 8篇 |
1993年 | 7篇 |
1992年 | 9篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 16篇 |
1988年 | 3篇 |
1987年 | 6篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 6篇 |
1979年 | 8篇 |
1978年 | 7篇 |
1977年 | 10篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1969年 | 3篇 |
排序方式: 共有699条查询结果,搜索用时 15 毫秒
81.
Previously, we reported that high PKCK2 activity could protect cancer cells from death receptor-mediated apoptosis through phosphorylation of procaspase-2. Because anoikis is another form of apoptosis, we asked whether PKCK2 could similarly confer resistance to anoikis on cancer cells. Human esophageal squamous cancer cell lines with high PKCK2 activity (HCE4 and HCE7) were anoikis-resistant, whereas cell lines with low PKCK2 activity (TE2 and TE3) were anoikis-sensitive. Because the cells showed different sensitivity to anoikis, we compared the expression of cell adhesion molecules between anoikis-sensitive TE2 and anoikis-resistant HCE4 cells using cDNA microarray. We found that E-cadherin is expressed only in TE2 cells; whereas N-cadherin is expressed instead of E-cadherin in HCE4 cells. To examine whether PKCK2 activity could determine the type of cadherin expressed, we first increased intracellular PKCK2 activity in TE2 cells by overexpressing the PKCK2α catalytic subunit using lentivirus and found that high PKCK2 activity could switch cadherin expression from type E to N and confer anoikis resistance. Conversely, a decrease in PKCK2 activity in HCE4 cells by knockdown of PKCK2α catalytic subunit using shRNA induced N- to E-cadherin switching and the anoikis-resistant cells became sensitive. In addition, N-cadherin expression correlated with PKB/Akt activation and increased invasiveness. We conclude that high intracellular PKCK2 activity confers anoikis resistance on esophageal cancer cells by inducing E- to N-cadherin switching. Mol Cancer Res; 10(8); 1032-8. ?2012 AACR. 相似文献
82.
83.
A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation 总被引:1,自引:0,他引:1
Erickson JR Joiner ML Guan X Kutschke W Yang J Oddis CV Bartlett RK Lowe JS O'Donnell SE Aykin-Burns N Zimmerman MC Zimmerman K Ham AJ Weiss RM Spitz DR Shea MA Colbran RJ Mohler PJ Anderson ME 《Cell》2008,135(3):462-474
tRNAs are synthesized as immature precursors, and on their way to functional maturity, extra nucleotides at their 5' ends are removed by an endonuclease called RNase P. All RNase P enzymes characterized so far are composed of an RNA plus one or more proteins, and tRNA 5' end maturation is considered a universal ribozyme-catalyzed process. Using a combinatorial purification/proteomics approach, we identified the components of human mitochondrial RNase P and reconstituted the enzymatic activity from three recombinant proteins. We thereby demonstrate that human mitochondrial RNase P is a protein enzyme that does not require a trans-acting RNA component for catalysis. Moreover, the mitochondrial enzyme turns out to be an unexpected type of patchwork enzyme, composed of a tRNA methyltransferase, a short-chain dehydrogenase/reductase-family member, and a protein of hitherto unknown functional and evolutionary origin, possibly representing the enzyme's metallonuclease moiety. Apparently, animal mitochondria lost the seemingly ubiquitous RNA world remnant after reinventing RNase P from preexisting components. 相似文献
84.
Structural basis for LEAFY floral switch function and similarity with helix-turn-helix proteins 总被引:1,自引:0,他引:1
Hamès C Ptchelkine D Grimm C Thevenon E Moyroud E Gérard F Martiel JL Benlloch R Parcy F Müller CW 《The EMBO journal》2008,27(19):2628-2637
The LEAFY (LFY) protein is a key regulator of flower development in angiosperms. Its gradually increased expression governs the sharp floral transition, and LFY subsequently controls the patterning of flower meristems by inducing the expression of floral homeotic genes. Despite a wealth of genetic data, how LFY functions at the molecular level is poorly understood. Here, we report crystal structures for the DNA-binding domain of Arabidopsis thaliana LFY bound to two target promoter elements. LFY adopts a novel seven-helix fold that binds DNA as a cooperative dimer, forming base-specific contacts in both the major and minor grooves. Cooperativity is mediated by two basic residues and plausibly accounts for LFY's effectiveness in triggering sharp developmental transitions. Our structure reveals an unexpected similarity between LFY and helix-turn-helix proteins, including homeodomain proteins known to regulate morphogenesis in higher eukaryotes. The appearance of flowering plants has been linked to the molecular evolution of LFY. Our study provides a unique framework to elucidate the molecular mechanisms underlying floral development and the evolutionary history of flowering plants. 相似文献
85.
Comparative LC-MS is a powerful method for detailed quantitative comparison of complex protein mixtures. Dedicated software is required for detection, matching, and alignment of peaks in multiple LC-MS datasets. However, retention time shifts, saturation effects, limitations of experimental accuracy, and possible occurrence of split peaks make it difficult for software to perfectly match all chromatograms. We describe a procedure to assess the above problems and show that dataset quality can be enhanced with the aid of cluster analysis. 相似文献
86.
87.
88.
M van Lith M van Ham A Griekspoor E Tjin D Verwoerd J Calafat H Janssen E Reits L Pastoors J Neefjes 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(2):884-892
MHC class II molecules bind antigenic peptides in the late endosomal/lysosomal MHC class II compartments (MIIC) before cell surface presentation. The class II modulatory molecules HLA-DM and HLA-DO mainly localize to the MIICs. Here we show that DM/DO complexes continuously recycle between the plasma membrane and the lysosomal MIICs. Like DMbeta and the class II-associated invariant chain, the DObeta cytoplasmic tail contains potential lysosomal targeting signals. The DObeta signals, however, are not essential for internalization of the DM/DO complex from the plasma membrane or targeting to the MIICs. Instead, the DObeta tail determines the distribution of both DM/DO and class II within the multivesicular MIIC by preferentially localizing them to the limiting membrane and, in lesser amounts, to the internal membranes. This distribution augments the efficiency of class II antigenic peptide loading by affecting the efficacy of lateral interaction between DM/DO and class II molecules. Sorting of DM/DO and class II molecules to specific localizations within the MIIC represents a novel way of regulating MHC class II Ag presentation. 相似文献
89.
90.