全文获取类型
收费全文 | 1889篇 |
免费 | 154篇 |
国内免费 | 1篇 |
出版年
2023年 | 4篇 |
2022年 | 26篇 |
2021年 | 39篇 |
2020年 | 13篇 |
2019年 | 23篇 |
2018年 | 34篇 |
2017年 | 26篇 |
2016年 | 60篇 |
2015年 | 108篇 |
2014年 | 119篇 |
2013年 | 118篇 |
2012年 | 185篇 |
2011年 | 145篇 |
2010年 | 96篇 |
2009年 | 92篇 |
2008年 | 125篇 |
2007年 | 118篇 |
2006年 | 98篇 |
2005年 | 85篇 |
2004年 | 99篇 |
2003年 | 92篇 |
2002年 | 86篇 |
2001年 | 20篇 |
2000年 | 20篇 |
1999年 | 21篇 |
1998年 | 28篇 |
1997年 | 14篇 |
1996年 | 18篇 |
1995年 | 8篇 |
1994年 | 13篇 |
1993年 | 13篇 |
1992年 | 10篇 |
1991年 | 7篇 |
1990年 | 8篇 |
1989年 | 7篇 |
1988年 | 3篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1970年 | 2篇 |
1967年 | 2篇 |
1966年 | 2篇 |
排序方式: 共有2044条查询结果,搜索用时 15 毫秒
991.
992.
993.
994.
Cornaciu I Boeszoermenyi A Lindermuth H Nagy HM Cerk IK Ebner C Salzburger B Gruber A Schweiger M Zechner R Lass A Zimmermann R Oberer M 《PloS one》2011,6(10):e26349
Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis. ATGL specifically hydrolyzes triacylglycerols (TGs), thereby generating diacylglycerols and free fatty acids. ATGL's enzymatic activity is co-activated by the protein comparative gene identification-58 (CGI-58) and inhibited by the protein G0/G1 switch gene 2 (G0S2). The enzyme is predicted to act through a catalytic dyad (Ser47, Asp166) located within the conserved patatin domain (Ile10-Leu178). Yet, neither an experimentally determined 3D structure nor a model of ATGL is currently available, which would help to understand how CGI-58 and G0S2 modulate ATGL's activity. In this study we determined the minimal active domain of ATGL. This minimal fragment of ATGL could still be activated and inhibited by CGI-58 and G0S2, respectively. Furthermore, we show that this minimal domain is sufficient for protein-protein interaction of ATGL with its regulatory proteins. Based on these data, we generated a 3D homology model for the minimal domain. It strengthens our experimental finding that amino acids between Leu178 and Leu254 are essential for the formation of a stable protein domain related to the patatin fold. Our data provide insights into the structure-function relationship of ATGL and indicate higher structural similarities in the N-terminal halves of mammalian patatin-like phospholipase domain containing proteins, (PNPLA1, -2,- 3 and -5) than originally anticipated. 相似文献
995.
996.
APC/C(Cdh1)-mediated degradation of the F-box protein NIPA is regulated by its association with Skp1
Klitzing Cv Huss R Illert AL Fröschl A Wötzel S Peschel C Bassermann F Duyster J 《PloS one》2011,6(12):e28998
NIPA (Nuclear Interaction Partner of Alk kinase) is an F-box like protein that targets nuclear Cyclin B1 for degradation. Integrity and therefore activity of the SCF(NIPA) E3 ligase is regulated by cell-cycle-dependent phosphorylation of NIPA, restricting substrate ubiquitination to interphase. Here we show that phosphorylated NIPA is degraded in late mitosis in an APC/C(Cdh1)-dependent manner. Binding of the unphosphorylated form of NIPA to Skp1 interferes with binding to the APC/C-adaptor protein Cdh1 and therefore protects unphosphorylated NIPA from degradation in interphase. Our data thus define a novel mode of regulating APC/C-mediated ubiquitination. 相似文献
997.
998.
999.
1000.
We present the results of a global study of dysregulated miRNAs in paired samples of normal mucosa and tumor from eight patients with colorectal cancer. Although there is existing data of miRNA contribution to colorectal tumorigenesis, these studies are typically small to medium scale studies of cell lines or non-paired tumor samples. The present study is to our knowledge unique in two respects. Firstly, the normal and adjacent tumor tissue samples are paired, thus taking into account the baseline differences between individuals when testing for differential expression. Secondly, we use high-throughput sequencing, thus enabling a comprehensive survey of all miRNAs expressed in the tissues. We use Illumina sequencing technology to perform sequencing and two different tools to statistically test for differences in read counts per gene between samples: edgeR when using the pair information and DESeq when ignoring this information, i.e., treating tumor and normal samples as independent groups. We identify 37 miRNAs that are significantly dysregulated in both statistical approaches, 19 down-regulated and 18 up-regulated. Some of these miRNAs are previously published as potential regulators in colorectal adenocarcinomas such as miR-1, miR-96 and miR-145. Our comprehensive survey of differentially expressed miRNAs thus confirms some existing findings. We have also discovered 16 dysregulated miRNAs, which to our knowledge have not previously been associated with colorectal carcinogenesis: the following significantly down-regulated miR-490-3p, -628-3p/-5p, -1297, -3151, -3163, -3622a-5p, -3656 and the up-regulated miR-105, -549, -1269, -1827, -3144-3p, -3177, -3180-3p, -4326. Although the study is preliminary with only eight patients included, we believe the results add to the present knowledge on miRNA dysregulation in colorectal carcinogenesis. As such the results would serve as a robust training set for validation of potential biomarkers in a larger cohort study. Finally, we also present data supporting the hypothesis that there are differences in miRNA expression between adenocarcinomas and neuroendocrine tumors of the colon. 相似文献