全文获取类型
收费全文 | 19197篇 |
免费 | 1412篇 |
国内免费 | 1525篇 |
专业分类
22134篇 |
出版年
2024年 | 48篇 |
2023年 | 332篇 |
2022年 | 661篇 |
2021年 | 1093篇 |
2020年 | 673篇 |
2019年 | 911篇 |
2018年 | 806篇 |
2017年 | 561篇 |
2016年 | 878篇 |
2015年 | 1155篇 |
2014年 | 1462篇 |
2013年 | 1523篇 |
2012年 | 1816篇 |
2011年 | 1570篇 |
2010年 | 992篇 |
2009年 | 850篇 |
2008年 | 945篇 |
2007年 | 810篇 |
2006年 | 658篇 |
2005年 | 579篇 |
2004年 | 486篇 |
2003年 | 436篇 |
2002年 | 387篇 |
2001年 | 286篇 |
2000年 | 290篇 |
1999年 | 303篇 |
1998年 | 195篇 |
1997年 | 199篇 |
1996年 | 189篇 |
1995年 | 151篇 |
1994年 | 136篇 |
1993年 | 96篇 |
1992年 | 140篇 |
1991年 | 114篇 |
1990年 | 100篇 |
1989年 | 77篇 |
1988年 | 53篇 |
1987年 | 31篇 |
1986年 | 28篇 |
1985年 | 41篇 |
1984年 | 18篇 |
1983年 | 23篇 |
1982年 | 12篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1965年 | 1篇 |
1963年 | 1篇 |
1962年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
11.
12.
Z He R Yamamoto E E Furth L J Schantz S L Naylor H George J T Billheimer J F Strauss 《DNA and cell biology》1991,10(8):559-569
Sterol carrier protein 2 (SCP2) is believed to play a key role in intracellular lipid movement. Here we report the cloning and nucleotide sequences of cDNAs encoding SCP2-related proteins of 58.85 kD and 30.8 kD and the assignment of the SCP2 gene to human chromosome 1 p21-pter. The SCP2-related proteins share common deduced carboxyl amino acid sequences with SCP2 and the cDNAs have a common 3' untranslated nucleotide sequence. The mRNAs encoding these proteins increased in a coordinate fashion as human placental cytotrophoblasts differentiated into syncytiotrophoblasts in culture. Our observations document the existence of a family of related proteins encoded by the human SCP2 gene. 相似文献
13.
14.
Bingqing Xia Xurui Shen Yang He Xiaoyan Pan Feng-Liang Liu Yi Wang Feipu Yang Sui Fang Yan Wu Zilei Duan Xiaoli Zuo Zhuqing Xie Xiangrui Jiang Ling Xu Hao Chi Shuangqu Li Qian Meng Hu Zhou Yubo Zhou Xi Cheng Xiaoming Xin Lin Jin Hai-Lin Zhang Dan-Dan Yu Ming-Hua Li Xiao-Li Feng Jiekai Chen Hualiang Jiang Gengfu Xiao Yong-Tang Zheng Lei-Ke Zhang Jingshan Shen Jia Li Zhaobing Gao 《Cell research》2021,31(8):847-860
Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.Subject terms: Cell death, Molecular biology 相似文献
15.
Qiang Lv Shuang Han Lei Wang Jinchan Xia Peng Li Ruoyang Hu Jinzheng Wang Lei Gao Yuli Chen Yu Wang Jing Du Fang Bao Yong Hu Xingzhi Xu Wei Xiao Yikun He 《Nucleic acids research》2022,50(12):6820
Nitric oxide (NO) is a key player in numerous physiological processes. Excessive NO induces DNA damage, but how plants respond to this damage remains unclear. We screened and identified an Arabidopsis NO hypersensitive mutant and found it to be allelic to TEBICHI/POLQ, encoding DNA polymerase θ. The teb mutant plants were preferentially sensitive to NO- and its derivative peroxynitrite-induced DNA damage and subsequent double-strand breaks (DSBs). Inactivation of TEB caused the accumulation of spontaneous DSBs largely attributed to endogenous NO and was synergistic to DSB repair pathway mutations with respect to growth. These effects were manifested in the presence of NO-inducing agents and relieved by NO scavengers. NO induced G2/M cell cycle arrest in the teb mutant, indicative of stalled replication forks. Genetic analyses indicate that Polθ is required for translesion DNA synthesis across NO-induced lesions, but not oxidation-induced lesions. Whole-genome sequencing revealed that Polθ bypasses NO-induced base adducts in an error-free manner and generates mutations characteristic of Polθ-mediated end joining. Our experimental data collectively suggests that Polθ plays dual roles in protecting plants from NO-induced DNA damage. Since Polθ is conserved in higher eukaryotes, mammalian Polθ may also be required for balancing NO physiological signaling and genotoxicity. 相似文献
16.
17.
18.
Weifeng He Yuan Gao Jing Zhou Yi Shi Dajing Xia Han-Ming Shen 《International journal of biological sciences》2022,18(12):4690
There is increasing amount of evidence indicating the close interplays between the replication cycle of SARS-CoV-2 and the autophagy-lysosome pathway in the host cells. While autophagy machinery is known to either assist or inhibit the viral replication process, the reciprocal effects of the SARS-CoV-2 on the autophagy-lysosome pathway have also been increasingly appreciated. More importantly, despite the disappointing results from the clinical trials of chloroquine and hydroxychloroquine in treatment of COVID-19, there is still ongoing effort in discovering new therapeutics targeting the autophagy-lysosome pathway. In this review, we provide an update-to-date summary of the interplays between the autophagy-lysosome pathway in the host cells and the pathogen SARS-CoV-2 at the molecular level, to highlight the prognostic value of autophagy markers in COVID-19 patients and to discuss the potential of developing novel therapeutic strategies for COVID-19 by targeting the autophagy-lysosome pathway. Thus, understanding the nature of such interactions between SARS-CoV-2 and the autophagy-lysosome pathway in the host cells is expected to provide novel strategies in battling against this global pandemic. 相似文献
19.
20.