首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   38887篇
  免费   3554篇
  国内免费   3624篇
  2024年   108篇
  2023年   495篇
  2022年   1111篇
  2021年   1848篇
  2020年   1290篇
  2019年   1577篇
  2018年   1512篇
  2017年   1172篇
  2016年   1589篇
  2015年   2358篇
  2014年   2785篇
  2013年   2987篇
  2012年   3613篇
  2011年   3162篇
  2010年   2108篇
  2009年   1730篇
  2008年   2246篇
  2007年   1956篇
  2006年   1689篇
  2005年   1492篇
  2004年   1300篇
  2003年   1174篇
  2002年   1130篇
  2001年   776篇
  2000年   616篇
  1999年   646篇
  1998年   392篇
  1997年   328篇
  1996年   353篇
  1995年   265篇
  1994年   329篇
  1993年   203篇
  1992年   267篇
  1991年   225篇
  1990年   217篇
  1989年   143篇
  1988年   110篇
  1987年   100篇
  1986年   83篇
  1985年   76篇
  1984年   69篇
  1983年   55篇
  1982年   52篇
  1981年   33篇
  1980年   25篇
  1979年   30篇
  1978年   23篇
  1976年   26篇
  1975年   27篇
  1974年   21篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Chen H  Sun H  You F  Sun W  Zhou X  Chen L  Yang J  Wang Y  Tang H  Guan Y  Xia W  Gu J  Ishikawa H  Gutman D  Barber G  Qin Z  Jiang Z 《Cell》2011,147(2):436-446
STAT6 plays a prominent role in adaptive immunity by transducing signals from extracellular cytokines. We now show that STAT6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger STING (also named MITA/ERIS) to recruit STAT6 to the endoplasmic reticulum, leading to STAT6 phosphorylation on Ser(407) by TBK1 and Tyr(641), independent of JAKs. Phosphorylated STAT6 then dimerizes and translocates to the nucleus to induce specific target genes responsible for immune cell homing. Virus-induced STAT6 activation is detected in all cell-types tested, in contrast to the cell-type specific role of STAT6 in cytokine signaling, and Stat6(-/-) mice are susceptible to virus infection. Thus, STAT6 mediates immune signaling in response to both cytokines at the plasma membrane, and virus infection at the endoplasmic reticulum.  相似文献   
992.
Indigenous Fe- and S-metabolizing bacteria play important roles both in the formation and the natural attenuation of acid mine drainage (AMD). Due to its low pH and Fe-S-rich waters, a river located in the Dabaoshan Mine area provides an ideal opportunity to study indigenous Fe- and S-metabolizing microbial communities and their roles in biogeochemical Fe and S cycling. In this work, water and sediment samples were collected from the river for physicochemical, mineralogical, and microbiological analyses. Illumina MiSeq sequencing indicated higher species richness in the sediment than in the water. Sequencing also found that Fe- and S-metabolizing bacteria were the dominant microorganisms in the heavily and moderately contaminated areas. Fe- and S-metabolizing bacteria found in the water were aerobes or facultative anaerobes, including Acidithiobacillus, Acidiphilium, Thiomonas, Gallionella, and Leptospirillum. Fe- and S-metabolizing bacteria found in the sediment belong to microaerobes, facultative anaerobes, or obligatory anaerobes, including Acidithiobacillus, Sulfobacillus, Thiomonas, Gallionella, Geobacter, Geothrix, and Clostridium. Among the dominant genera in the sediment, Geobacter and Geothrix were rarely detected in AMD-contaminated natural environments. Canonical correspondence analysis indicated that pH, S, and Fe concentration gradients were the most important factors in structuring the river microbial community. Moreover, a scheme explaining the biogeochemical Fe and S cycling is advanced in light of the Fe and S species distribution and the identified Fe- and S-metabolizing bacteria.  相似文献   
993.
Lu J  Sivamani E  Li X  Qu R 《Plant cell reports》2008,27(10):1587-1600
Ubiquitin is an abundant protein involved in protein degradation and cell cycle control in plants and rubi3 is a polyubiquitin gene isolated from rice (Oryza sativa L.). Using both GFP and GUS as reporter genes, we analyzed the expression pattern of the rubi3 promoter as well as the effects of the rubi3 5'-UTR (5' untranslated region) intron and the 5' terminal 27 bp of the rubi3 coding sequence on the activity of the promoter in transgenic rice plants. The rubi3 promoter with the 5'-UTR intron was active in all the tissue and cell types examined and supported more constitutive expression of reporter genes than the maize Ubi-1 promoter. The rubi3 5'-UTR intron mediated enhancement on the activity of its promoter in a tissue-specific manner but did not alter its overall expression pattern. The enhancement was particularly intense in roots, pollen grains, inner tissue of ovaries, and embryos and aleurone layers in maturing seeds. The translational fusion of the first 27 bp of the rubi3 coding sequence to GUS gene further enhanced GUS expression directed by the rubi3 promoter in all the tissues examined. The rubi3 promoter should be an important addition to the arsenal of strong and constitutive promoters for monocot transformation and biotechnology.  相似文献   
994.
Gao F  Yi J  Yuan JQ  Shi GY  Tang XM 《Cell research》2004,14(1):81-85
Double staining flow cytometry was performed using 7-amino actinomycin D and 6-carboxy-2‘,7‘-dichlorodihydrofluorescein diacetate, to detect the level fluctuation of reactive oxygen species (ROS) during the cell cycle of normal NB4 cells. Our results showed that NB4 cells possessed higher level of ROS in G2/M phase than in G1 and S phases. Double staining flow cytometry, with TdT mediated dUTP nick end labeling (Tunel) and propidium iodide(PI), indicated that As2O3 (2μM) could induce apoptosis in NB4 cells prevailingly from G2/M phase, and this efficacy was enhanced upon co-administration of 2, 3-dimethoxy-1, 4-naphthoquinone (DMNQ) (2.5μM) which could produce the endogenous ROS. These results suggested that different ROS level in different cell cycle phases of NB4 cells might determin the selective induction of G2/M apoptosis and the cells‘ susceptibility to apoptosis by As2O3.  相似文献   
995.
转Bt基因作物种植对土壤养分含量的影响   总被引:12,自引:0,他引:12  
转Bt基因棉花和水稻的盆栽种植试验结果表明,与非转Bt基因原始对照相比,转Bt基因水稻短期种植30 d和转Bt基因棉花种植一个生长季后土壤中全碳和全氮以及碱解氮、速效磷、有效硫含量与对照均无显著差异,表明转Bt基因作物的种植短期内对土壤主要营养元素循环和平衡的扰动是微小的.  相似文献   
996.
目的研究阿尔茨海默病(Alzheimer disease,AD)模型小鼠APP/PS1转基因小鼠脑内锌转运体ZNT7的分布和表达,探讨ZNT7参与Aβ老年斑形成的机理。方法应用免疫组织化学染色观察ZNT7在脑内分布情况,应用Western Blot方法分析ZNT7在APP/PS1转基因小鼠大脑内的表达。结果ZNT7免疫阳性反应产物主要分布在APP/PS1转基因小鼠大脑皮层、纹状体和海马的老年斑内,强阳性的ZNT7免疫产物定位于老年斑的核心。Western Blot分析结果表明ZNT7在APP/PS1转基因小鼠大脑内的表达明显高于野生型小鼠。结论ZNT7在APP/PS1转基因小鼠大脑内的高表达以及在Aβ老年斑的定位,提示ZNT7可能参与了锌离子在老年斑内的聚集,进而参与了APP/PS1转基因小鼠大脑内老年斑的形成。  相似文献   
997.
随着超声技术的发展和对心脏疾病治疗研究的深入,超声技术在心脏疾病治疗领域中的应用逐步成为研究热点。其中,体外超声作为一种无创物理疗法,尤为受到研究者们的关注。本文介绍了近年来体外超声在心脏疾病治疗中的应用进展,并对其存在的问题和发展前景进行了探讨。  相似文献   
998.
血管紧张素转换酶2(ACE2)和Mas受体的发现使人们对肾素-血管紧张素(RAS)有了更全面的认识。ACE2可水解血管紧张素Ⅰ和血管紧张素Ⅱ直接或间接生成血管紧张素1-7(Ang 1-7),并与高血压的形成密切相关。Ang 1-7主要通过Mas受体引起血管舒张、抑制细胞增殖。ACE2-Ang1-7-Mas轴的发现为RAS的研究、高血压等心血管疾病的防治和新药开发提供了新的思路和方向。  相似文献   
999.
Lu HM  Yin DC  Xu C 《生理科学进展》2009,40(4):292-296
药物成瘾危害人类健康并带来经济和社会问题,而滥用药物所造成的身体损害、身体依赖和戒断综合征的治疗等问题的解决仍存在困难.涡虫具有原始的中枢神经系统,其神经递质系统与哺乳类相似,具有易观察可量化的戒断反应,具有易饲养、低成本、无伦理问题等优于哺乳类实验动物的特点,因而迅速成为新的神经药理学在体动物实验模型.本文对涡虫的优点及其在药物成瘾机制等方面的研究进展进行综述,为药物成瘾机制及其治疗的研究提供新的思路.  相似文献   
1000.
Secreted modular calcium-binding protein-2 (SMOC-2) is a recently-identified SPARC-related protein of unknown function. In mRNA profiling experiments we, found that SMOC-2 expression was elevated in quiescent (G0) mouse fibroblasts and repressed after mitogenic stimulation with serum. The G0-specific expression of SMOC-2 was similar to that of platelet-derived growth factor-beta receptor (PDGFbetaR), a major mitogenic receptor. Therefore, we tested a possible role for SMOC-2 in growth factor-induced cell cycle progression. SMOC-2 overexpression augmented DNA synthesis induced by serum and fibroblast mitogens (including PDGF-BB and basic fibroblast growth factor). Conversely, SMOC-2 ablation by using small interfering RNA attenuated DNA synthesis in response to PDGF-BB and other growth factors. Mitogen-induced expression of cyclin D1 was attenuated in SMOC-2-ablated cells, and cyclin D1-overexpressing cells were resistant to inhibition of mitogenesis after SMOC-2 ablation. Therefore, cyclin D1 is limiting for G1 progression in SMOC-2-deficient cells. SMOC-2 ablation did not inhibit PDGF-induced PDGFbetaR autophosphorylation or PDGF-BB-dependent activation of mitogen-activated protein kinase and Akt kinases, suggesting that SMOC-2 is dispensable for growth factor receptor activation. However, integrin-linked kinase (ILK) activity was reduced in SMOC-2-ablated cells. Ectopic expression of hyperactive ILK corrected the defective mitogenic response of SMOC-2-deficient cells. Therefore, SMOC-2 contributes to cell cycle progression by maintaining ILK activity during G1. These results identify a novel role for SMOC-2 in cell cycle control.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号