全文获取类型
收费全文 | 16303篇 |
免费 | 1252篇 |
国内免费 | 1503篇 |
出版年
2024年 | 26篇 |
2023年 | 192篇 |
2022年 | 503篇 |
2021年 | 936篇 |
2020年 | 616篇 |
2019年 | 754篇 |
2018年 | 647篇 |
2017年 | 512篇 |
2016年 | 718篇 |
2015年 | 1009篇 |
2014年 | 1211篇 |
2013年 | 1304篇 |
2012年 | 1518篇 |
2011年 | 1304篇 |
2010年 | 812篇 |
2009年 | 808篇 |
2008年 | 899篇 |
2007年 | 763篇 |
2006年 | 664篇 |
2005年 | 502篇 |
2004年 | 509篇 |
2003年 | 469篇 |
2002年 | 344篇 |
2001年 | 280篇 |
2000年 | 255篇 |
1999年 | 271篇 |
1998年 | 163篇 |
1997年 | 131篇 |
1996年 | 132篇 |
1995年 | 129篇 |
1994年 | 124篇 |
1993年 | 70篇 |
1992年 | 98篇 |
1991年 | 86篇 |
1990年 | 71篇 |
1989年 | 45篇 |
1988年 | 35篇 |
1987年 | 38篇 |
1986年 | 27篇 |
1985年 | 45篇 |
1984年 | 12篇 |
1983年 | 10篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 406 毫秒
1.
Peng Wang Ronghua Luo Min Zhang Yaqing Wang Tianzhang Song Tingting Tao Zhongyu Li Lin Jin Hongyi Zheng Wenwen Chen Mengqian Zhao Yongtang Zheng Jianhua Qin 《Cell death & disease》2020,11(12)
COVID-19, caused by SARS-CoV-2, is an acute and rapidly developing pandemic, which leads to a global health crisis. SARS-CoV-2 primarily attacks human alveoli and causes severe lung infection and damage. To better understand the molecular basis of this disease, we sought to characterize the responses of alveolar epithelium and its adjacent microvascular endothelium to viral infection under a co-culture system. SARS-CoV-2 infection caused massive virus replication and dramatic organelles remodeling in alveolar epithelial cells, alone. While, viral infection affected endothelial cells in an indirect manner, which was mediated by infected alveolar epithelium. Proteomics analysis and TEM examinations showed viral infection caused global proteomic modulations and marked ultrastructural changes in both epithelial cells and endothelial cells under the co-culture system. In particular, viral infection elicited global protein changes and structural reorganizations across many sub-cellular compartments in epithelial cells. Among the affected organelles, mitochondrion seems to be a primary target organelle. Besides, according to EM and proteomic results, we identified Daurisoline, a potent autophagy inhibitor, could inhibit virus replication effectively in host cells. Collectively, our study revealed an unrecognized cross-talk between epithelium and endothelium, which contributed to alveolar–capillary injury during SARS-CoV-2 infection. These new findings will expand our understanding of COVID-19 and may also be helpful for targeted drug development.Subject terms: Mechanisms of disease, Viral infection 相似文献
2.
3.
4.
5.
6.
Tristan J. Iseli Nigel Turner Xiao-Yi Zeng Gregory J. Cooney Edward W. Kraegen Sheng Yao Yang Ye David E. James Ji-Ming Ye 《PloS one》2013,8(4)
We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo. Here we interrogated the mechanism by which these novel compounds activate AMPK, a leading anti-diabetic drug target. BMTs did not activate AMPK directly in an allosteric manner as AMP or the Abbott compound (A-769662) does, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications. BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20–35%. Incubation with the CaMKKβ inhibitor, STO-609, completely attenuated this effect suggesting a key role for CaMKKβ in this activation. Incubation of L6 myotubes with the calcium chelator EGTA-AM did not alter this activation suggesting that the BMT-dependent activation was Ca2+-independent. We therefore propose that CaMKKβ is a key upstream kinase for BMT-induced activation of AMPK. 相似文献
7.
The mechanical properties of human lung tissue were measured in a state of biaxial tension. The experimental data were fitted with a pseudo-elastic constitutive equation proposed earlier and the physical constants were identified. 相似文献
8.
9.
10.
Molecular genetics of phenylketonuria in Orientals: linkage disequilibrium between a termination mutation and haplotype 4 of the phenylalanine hydroxylase gene. 总被引:11,自引:8,他引:3
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
T Wang Y Okano R Eisensmith S Z Huang Y T Zeng W H Lo S L Woo 《American journal of human genetics》1989,45(5):675-680
Phenylketonuria (PKU) is a common metabolic disorder among Chinese, with a prevalence of about 1 in 16,500 births. This frequency is very similar to that among Caucasians. Individual exons of the phenylalanine hydroxylase (PAH) gene with flanking introns were amplified by polymerase chain reaction and cloned into M13 for sequence analysis. An Arg111-to-Ter111 mutation has been identified in exon 3 of the PAH gene in a Chinese PKU patient. The mutation is in linkage disequilibrium with the mutant haplotype 4 alleles which are the most prevalent haplotype among the Orientals. The mutation accounts for about 10% of the Chinese PKU alleles and is absent from the Caucasians, demonstrating that independent mutational events have occurred in the PAH locus after racial divergence. 相似文献