全文获取类型
收费全文 | 8279篇 |
免费 | 746篇 |
国内免费 | 828篇 |
出版年
2024年 | 11篇 |
2023年 | 136篇 |
2022年 | 188篇 |
2021年 | 458篇 |
2020年 | 395篇 |
2019年 | 457篇 |
2018年 | 383篇 |
2017年 | 308篇 |
2016年 | 384篇 |
2015年 | 546篇 |
2014年 | 651篇 |
2013年 | 673篇 |
2012年 | 797篇 |
2011年 | 679篇 |
2010年 | 448篇 |
2009年 | 398篇 |
2008年 | 419篇 |
2007年 | 350篇 |
2006年 | 295篇 |
2005年 | 282篇 |
2004年 | 221篇 |
2003年 | 204篇 |
2002年 | 176篇 |
2001年 | 145篇 |
2000年 | 126篇 |
1999年 | 114篇 |
1998年 | 72篇 |
1997年 | 56篇 |
1996年 | 58篇 |
1995年 | 51篇 |
1994年 | 42篇 |
1993年 | 36篇 |
1992年 | 41篇 |
1991年 | 30篇 |
1990年 | 32篇 |
1989年 | 25篇 |
1988年 | 20篇 |
1987年 | 17篇 |
1986年 | 11篇 |
1985年 | 13篇 |
1984年 | 5篇 |
1983年 | 14篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1979年 | 8篇 |
1973年 | 6篇 |
1972年 | 11篇 |
1971年 | 7篇 |
1970年 | 7篇 |
1968年 | 7篇 |
排序方式: 共有9853条查询结果,搜索用时 203 毫秒
1.
2.
Janne Alahuhta Sarian Kosten Munemitsu Akasaka Dominique Auderset Mattia M. Azzella Rossano Bolpagni Claudia P. Bove Patricia A. Chambers Eglantine Chappuis John Clayton Mary de Winton Frauke Ecke Esperança Gacia Gana Gecheva Patrick Grillas Jennifer Hauxwell Seppo Hellsten Jan Hjort Mark V. Hoyer Christiane Ilg Agnieszka Kolada Minna Kuoppala Torben Lauridsen En Hua Li Balázs A. Lukács Marit Mjelde Alison Mikulyuk Roger P. Mormul Jun Nishihiro Beat Oertli Laila Rhazi Mouhssine Rhazi Laura Sass Christine Schranz Martin Søndergaard Takashi Yamanouchi Qing Yu Haijun Wang Nigel Willby Xiao Ke Zhang Jani Heino 《Journal of Biogeography》2017,44(8):1758-1769
3.
This paper proposes a modified BFGS formula using a trust region model for solving nonsmooth convex minimizations by using the Moreau-Yosida regularization (smoothing) approach and a new secant equation with a BFGS update formula. Our algorithm uses the function value information and gradient value information to compute the Hessian. The Hessian matrix is updated by the BFGS formula rather than using second-order information of the function, thus decreasing the workload and time involved in the computation. Under suitable conditions, the algorithm converges globally to an optimal solution. Numerical results show that this algorithm can successfully solve nonsmooth unconstrained convex problems. 相似文献
4.
Du Jingjing Qv Mingxiang Li Ke Yin Xiaoyun Meng Fanxiao Yang Jingchao Ma Chuang 《Limnology》2019,20(2):173-179
Limnology - The impacts of three commonly used benzophenone-type UV filters including benzophenone (BP), 2-hydroxy-4-methoxy-benzophenone (BP3), and 2-hydroxy-4-methoxy-benzophenone-5-sulfonicacid... 相似文献
5.
6.
7.
Cong Wang Liping Jiang Saiqi Wang Hongge Shi Junwei Wang Ran Wang Yongmei Li Yinhui Dou Ying Liu Guiqin Hou Yu Ke Hongmin Liu 《PloS one》2015,10(6)
Jesridonin, a small molecule obtained through the structural modification of Oridonin, has extensive antitumor activity. In this study, we evaluated both its in vitro activity in the cancer cell line EC109 and its in vivo effect on tumor xenografts in nude mice. Apoptosis induced by Jesridonin was determined using an MTT assay, Annexin-V FITC assay and Hoechest 33258 staining. Apoptosis via mitochondrial and death receptor pathways were confirmed by detecting the regulation of MDM2, p53, and Bcl-2 family members and by activation of caspase-3/-8/-9. In addition, vena caudalis injection of Jesridonin showed significant inhibition of tumor growth in the xenograft model, and Jesridonin-induced cell apoptosis in tumor tissues was determined using TUNEL. Biochemical serum analysis of alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), total protein (TP) and albumin (ALB) indicated no obvious effects on liver function. Histopathological examination of the liver, kidney, lung, heart and spleen revealed no signs of JD-induced toxicity. Taken together, these results demonstrated that Jesridonin exhibits antitumor activity in human esophageal carcinomas EC109 cells both in vitro and in vivo and demonstrated no adverse effects on major organs in nude mice. These studies provide support for new drug development. 相似文献
8.
Patrick L. Leslie Hengming Ke Yanping Zhang 《The Journal of biological chemistry》2015,290(20):12941-12950
The oncoprotein murine double minute 2 (MDM2) is an E3 ligase that plays a prominent role in p53 suppression by promoting its polyubiquitination and proteasomal degradation. In its active form, MDM2 forms homodimers as well as heterodimers with the homologous protein murine double minute 4 (MDMX), both of which are thought to occur through their respective C-terminal RING (really interesting new gene) domains. In this study, using multiple MDM2 mutants, we show evidence suggesting that MDM2 homo- and heterodimerization occur through distinct mechanisms because MDM2 RING domain mutations that inhibit MDM2 interaction with MDMX do not affect MDM2 interaction with WT MDM2. Intriguingly, deletion of a portion of the MDM2 central acidic domain selectively inhibits interaction with MDM2 while leaving intact the ability of MDM2 to interact with MDMX and to ubiquitinate p53. Further analysis of an MDM2 C-terminal deletion mutant reveals that the C-terminal residues of MDM2 are required for both MDM2 and MDMX interaction. Collectively, our results suggest a model in which MDM2-MDMX heterodimerization requires the extreme C terminus and proper RING domain structure of MDM2, whereas MDM2 homodimerization requires the extreme C terminus and the central acidic domain of MDM2, suggesting that MDM2 homo- and heterodimers utilize distinct MDM2 domains. Our study is the first to report mutations capable of separating MDM2 homo- and heterodimerization. 相似文献
9.
Haoyu Liang Lin Jiang Qiyun Jiang Jie Shi Jingxi Xiang Xiaohui Yan Xiangcheng Zhu Lixing Zhao Ben Shen Yanwen Duan Yong Huang 《Environmental microbiology》2019,21(11):4270-4282
Acyltransferase (AT)-less type I polyketide synthases (PKSs) produce complex natural products due to the presence of many unique tailoring enzymes. The 3-hydroxy-3-methylglutaryl coenzyme A synthases (HCSs) are responsible for β-alkylation of the growing polyketide intermediates in AT-less type I PKSs. In this study, we discovered a large group of HCSs, closely associated with the characterized and orphan AT-less type I PKSs through in silico genome mining, sequence and genome neighbourhood network analyses. Using HCS-based probes, the survey of 1207 in-house strains and 18 soil samples from different geographic locations revealed the vast diversity of HCS-containing AT-less type I PKSs. The presence of HCSs in many AT-less type I PKSs suggests their co-evolutionary relationship. This study provides a new probe to study the abundance and diversity of AT-less type I PKSs in the environment and microbial strain collections. Our study should inspire future efforts to discover new polyketide natural products from AT-less type I PKSs. 相似文献
10.
Kai Ren Buying Li Zhenhua Liu Lin Xia Mengen Zhai Xufeng Wei Weixun Duan Shiqiang Yu 《Journal of cellular and molecular medicine》2021,25(10):4623-4636
Thoracic aortic dissection (TAD) is an aortic disease associated with dysregulated extracellular matrix composition and de-differentiation of vascular smooth muscle cells (SMCs). Growth Differentiation Factor 11 (GDF11) is a member of transforming growth factor β (TGF-β) superfamily associated with cardiovascular diseases. The present study attempted to investigate the expression of GDF11 in TAD and its effects on aortic SMC phenotype transition. GDF11 level was found lower in the ascending thoracic aortas of TAD patients than healthy aortas. The mouse model of TAD was established by β-aminopropionitrile monofumarate (BAPN) combined with angiotensin II (Ang II). The expression of GDF11 was also decreased in thoracic aortic tissues accompanied with increased inflammation, arteriectasis and elastin degradation in TAD mice. Administration of GDF11 mitigated these aortic lesions and improved the survival rate of mice. Exogenous GDF11 and adeno-associated virus type 2 (AAV-2)-mediated GDF11 overexpression increased the expression of contractile proteins including ACTA2, SM22α and myosin heavy chain 11 (MYH11) and decreased synthetic markers including osteopontin and fibronectin 1 (FN1), indicating that GDF11 might inhibit SMC phenotype transition and maintain its contractile state. Moreover, GDF11 inhibited the production of matrix metalloproteinase (MMP)-2, 3, 9 in aortic SMCs. The canonical TGF-β (Smad2/3) signalling was enhanced by GDF11, while its inhibition suppressed the inhibitory effects of GDF11 on SMC de-differentiation and MMP production in vitro. Therefore, we demonstrate that GDF11 may contribute to TAD alleviation via inhibiting inflammation and MMP activity, and promoting the transition of aortic SMCs towards a contractile phenotype, which provides a therapeutic target for TAD. 相似文献