全文获取类型
收费全文 | 28403篇 |
免费 | 2571篇 |
国内免费 | 2085篇 |
出版年
2024年 | 7篇 |
2023年 | 271篇 |
2022年 | 409篇 |
2021年 | 1341篇 |
2020年 | 1012篇 |
2019年 | 1200篇 |
2018年 | 1201篇 |
2017年 | 898篇 |
2016年 | 1251篇 |
2015年 | 1736篇 |
2014年 | 2000篇 |
2013年 | 2183篇 |
2012年 | 2667篇 |
2011年 | 2297篇 |
2010年 | 1422篇 |
2009年 | 1264篇 |
2008年 | 1494篇 |
2007年 | 1310篇 |
2006年 | 1137篇 |
2005年 | 1036篇 |
2004年 | 924篇 |
2003年 | 862篇 |
2002年 | 762篇 |
2001年 | 652篇 |
2000年 | 531篇 |
1999年 | 501篇 |
1998年 | 296篇 |
1997年 | 300篇 |
1996年 | 281篇 |
1995年 | 260篇 |
1994年 | 247篇 |
1993年 | 144篇 |
1992年 | 227篇 |
1991年 | 160篇 |
1990年 | 141篇 |
1989年 | 116篇 |
1988年 | 86篇 |
1987年 | 99篇 |
1986年 | 61篇 |
1985年 | 63篇 |
1984年 | 44篇 |
1983年 | 35篇 |
1982年 | 33篇 |
1981年 | 21篇 |
1980年 | 11篇 |
1979年 | 11篇 |
1978年 | 6篇 |
1973年 | 6篇 |
1969年 | 5篇 |
1967年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
1.
ObjectiveWe investigated whether glutamate, NMDA receptors, and eukaryote elongation factor-2 kinase (eEF-2K)/eEF-2 regulate P-glycoprotein expression, and the effects of the eEF-2K inhibitor NH125 on the expression of P-glycoprotein in rat brain microvessel endothelial cells (RBMECs).MethodsCortex was obtained from newborn Wistar rat brains. After surface vessels and meninges were removed, the pellet containing microvessels was resuspended and incubated at 37°C in culture medium. Cell viability was assessed by the MTT assay. RBMECs were identified by immunohistochemistry with anti-vWF. P-glycoprotein, phospho-eEF-2, and eEF-2 expression were determined by western blot analysis. Mdr1a gene expression was analyzed by RT-PCR.ResultsMdr1a mRNA, P-glycoprotein and phospho-eEF-2 expression increased in L-glutamate stimulated RBMECs. P-glycoprotein and phospho-eEF-2 expression were down-regulated after NH125 treatment in L-glutamate stimulated RBMECs.ConclusionseEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent. 相似文献
2.
3.
Wang Ting-Ting Zhu Chen-Ye Zheng Shuang Meng Cai-Cai Wang Tian-Tian Meng Dan-Hua Li Yi-Jun Zhu Hao-Miao Wang Feng-Shan Sheng Ju-Zheng 《Applied microbiology and biotechnology》2018,102(11):4785-4797
Applied Microbiology and Biotechnology - Avibacterium paragallinarum is a Gram-negative bacterium that causes infectious coryza in chicken. It was reported that the capsule polysaccharides... 相似文献
4.
Bin Zhu Chongwen Yang Hongrong Liu Lingpeng Cheng Feng Song Songjun Zeng Xiaojun Huang Gang Ji Ping Zhu 《Journal of molecular biology》2014
Many double-stranded RNA (dsRNA) viruses are capable of transcribing and capping RNA within a stable icosahedral viral capsid. The turret of turreted dsRNA viruses belonging to the family Reoviridae is formed by five copies of the turret protein, which contains domains with both 7-N-methyltransferase and 2′-O-methyltransferase activities, and serves to catalyze the methylation reactions during RNA capping. Cypovirus of the family Reoviridae provides a good model system for studying the methylation reactions in dsRNA viruses. Here, we present the structure of a transcribing cypovirus to a resolution of ~ 3.8 Å by cryo-electron microscopy. The binding sites for both S-adenosyl-l-methionine and RNA in the two methyltransferases of the turret were identified. Structural analysis of the turret in complex with RNA revealed a pathway through which the RNA molecule reaches the active sites of the two methyltransferases before it is released into the cytoplasm. The pathway shows that RNA capping reactions occur in the active sites of different turret protein monomers, suggesting that RNA capping requires concerted efforts by at least three turret protein monomers. Thus, the turret structure provides novel insights into the precise mechanisms of RNA methylation. 相似文献
5.
6.
7.
8.
9.
Hui-juan Zhu Lin-jie Wang Xiang-qing Wang Hui Pan Nai-shi Li Hong-bo Yang Ming Jin Bao-xia Zang Feng-ying Gong 《Cytotechnology》2015,67(5):885-892
Hydroxysafflor yellow A (HSYA), a main component of safflor yellow, has been demonstrated to prevent steroid-induced avascular necrosis of femoral head by inhibiting primary bone marrow-derived mesenchymal stromal cells adipogenic differentiation induced by steroid. In this study, we investigate the effect of HSYA on the proliferation and adipogenesis of mouse 3T3-L1 preadipocytes. The effects of HSYA on proliferation and differentiation of 3T3-L1 cells and its possible mechanism were studied by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide spectrophotometry, Oil Red O staining, intracellular triglyceride assays, real-time quantitative RT-PCR, transient transfection and dual luciferase reporter gene methods. HSYA inhibited the proliferation of 3T3-L1 preadipocytes and cell viability greatly decreased in a dose and time dependent manner. HSYA (1 mg/l) notably reduced the amount of intracellular lipid and triglyceride content in adipocytes by 21.3 % (2.13 ± 0.36 vs 2.71 ± 0.40, P < 0.01) and 22.6 % (1.33 ± 0.07 vs 1.72 ± 0.07, P < 0.01) on days 8 following the differentiation, respectively. HSYA (1 mg/l) significantly increased hormone-sensitive lipase (HSL) mRNA expression and promoter activities by 2.4- and 1.55-fold, respectively (P < 0.01), in differentiated 3T3-L1 adipocytes. HSYA inhibits the proliferation and adipogenesis of 3T3-L1 preadipocytes. The inhibitory action of HYSA on adipogenesis may be due to the promotion of lipolytic-specific enzyme HSL expression by increasing HSL promoter activity. 相似文献
10.
M.S. Meah M. Lertcanawanichakul P. Pedpradab W. Lin K. Zhu G. Li P. Panichayupakaranant 《Letters in applied microbiology》2020,71(5):510-519
α-Mangostin-rich extract (AME) exhibited satisfactory inhibitory activities against all tested MRSA strains, with minimum inhibitory concentrations (MICs) of 7·8–31·25 µg ml−1, whereas lawsone methyl ether (LME) and ampicillin revealed weak antibacterial activity with MICs of 62·5–125 µg ml−1. However, the combination of AME and LME showed synergistic effects against all tested MRSA strains with fractional inhibitory concentration index (FICI) values of 0·008–0·009, while the combination of AME and ampicillin, as well as LME and ampicillin produced synergistic effects with FICIs of 0·016–0·257. A time-kill assay against MRSA (DMST 20654 strain) revealed a 6-log reduction in CFU per ml, which completely inhibited bacterial growth for the combinations of AME and LME, AME and ampicillin, and LME and ampicillin at a 8-h incubation, while those against MRSA (2468 strain) were at 10-h incubation. The combination of α-mangostin and LME as well as the combinations of each compound with ampicillin synergized the alteration of membrane permeability. In addition, α-mangostin, LME and ampicillin inhibited the biofilm formation of MRSA. These findings indicated that the combinations of AME and LME or each of them in combination with ampicillin had enhanced antibacterial activity against MRSA. Therefore, these compounds might be used as the antibacterial cocktails for treatment of MRSA. 相似文献