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   4956篇
  免费   543篇
  国内免费   818篇
  6317篇
  2024年   29篇
  2023年   139篇
  2022年   209篇
  2021年   338篇
  2020年   251篇
  2019年   316篇
  2018年   251篇
  2017年   186篇
  2016年   302篇
  2015年   372篇
  2014年   432篇
  2013年   456篇
  2012年   472篇
  2011年   470篇
  2010年   281篇
  2009年   232篇
  2008年   276篇
  2007年   204篇
  2006年   165篇
  2005年   122篇
  2004年   122篇
  2003年   118篇
  2002年   110篇
  2001年   78篇
  2000年   54篇
  1999年   58篇
  1998年   36篇
  1997年   40篇
  1996年   26篇
  1995年   21篇
  1994年   22篇
  1993年   24篇
  1992年   23篇
  1991年   17篇
  1990年   20篇
  1989年   4篇
  1988年   6篇
  1987年   7篇
  1986年   7篇
  1985年   6篇
  1984年   7篇
  1983年   3篇
  1982年   2篇
  1980年   1篇
  1979年   1篇
  1950年   1篇
排序方式: 共有6317条查询结果,搜索用时 0 毫秒
41.
Cui  Guibin  Zhao  Yanfeng  Zhang  Jialing  Chao  Manning  Xie  Kunliang  Zhang  Chao  Sun  Fengli  Liu  Shudong  Xi  Yajun 《Plant molecular biology》2019,100(4-5):391-410
Plant Molecular Biology - Our results reveal both soil drought and PEG can enhance malate, glutathione and ascorbate metabolism, and proline biosynthesis, whereas soil drought induced these...  相似文献   
42.
43.
With the development of mass spectrometry (MS)-based proteomics technologies, patient-derived xenograft (PDX), which is generated from the primary tumor of a patient, is widely used for the proteome-wide analysis of cancer mechanism and biomarker identification of a drug. However, the proteomics data interpretation is still challenging due to complex data deconvolution from the PDX sample that is a cross-species mixture of human cancerous tissues and immunodeficient mouse tissues. In this study, by using the lab-assembled mixture of human and mouse cells with different mixing ratios as a benchmark, we developed and evaluated a new method, SPA (shared peptide allocation), for protein quantitation by considering the unique and shared peptides of both species. The results showed that SPA could provide more convenient and accurate protein quantitation in human–mouse mixed samples. Further validation on a pair of gastric PDX samples (one bearing FGFR2 amplification while the other one not) showed that our new method not only significantly improved the overall protein identification, but also detected the differential phosphorylation of FGFR2 and its downstream mediators (such as RAS and ERK) exclusively. The tool pdxSPA is freely available at https://github.com/Li-Lab-Proteomics/pdxSPA.  相似文献   
44.
Genetically engineered mice provide an excellent tool to study the role of a particular gene in biological systems and will be increasingly used as models to understand the signal transduction mechanisms involved in ischemic preconditioning (IP). However, the phenomenon of IP has not been well characterized in this species. We therefore attempted to examine whether IP could protect isolated mouse heart against global ischemia/reperfusion (GI/R) injury. Thirty adult mice hearts were perfused at constant pressure of 55 mmHg in Langendorff mode. Following 20 min equilibration, the hearts were randomized into three groups (n = 10/each): (1) Control Group; (2) IP2.5 Group: IP with two cycles of 2.5 min GI + 2.5 min R; (3) IP5 Group: IP with 5 min GI + 5 min R. All hearts were then subjected to 20 min of GI and 30 min R (37°C). Ventricular developed force was measured by a force transducer attached to the apex. Leakage of CK and LDH was measured in coronary efflux. Infarct size was determined by tetrazolium staining. Following sustained GI/R, infarct size was significantly reduced in IP2.5 (13.8 ± 2.3%), but not in IP5 (20.1 ± 4.0%), when compared with non-preconditioned control (23.6 ± 3.8%) hearts. CK and LDH release was also reduced in both IP2.5 and IP5 groups. No significant improvement in post-ischemic ventricular contractile function was observed in either IP groups. We conclude that IP with repetitive cycles of brief GI/R is able to reduce myocardial infarct size and intracellular enzyme leakage caused by a sustained GI/R in the isolated perfused mouse heart. This anti-necrosis cardioprotection induced by IP was not associated with the amelioration of post-ischemic ventricular dysfunction.  相似文献   
45.
alphaB-Crystallin, a major protein of lens fiber cells, is a stress-induced chaperone expressed at low levels in the lens epithelium and numerous other tissues, and its expression is enhanced in certain pathological conditions. However, the function of alphaB in these tissues is not known. Lenses of alphaB-/- mice develop degeneration of specific skeletal muscles but do not develop cataracts. Recent work in our laboratory indicates that primary cultures of alphaB-/- lens epithelial cells demonstrate genomic instability and undergo hyperproliferation at a frequency 4 orders of magnitude greater than that predicted by spontaneous immortalization of rodent cells. We now demonstrate that the hyperproliferative alphaB-/- lens epithelial cells undergo phenotypic changes that include the appearance of the p53 protein as shown by immunoblot analysis. Sequence analysis showed a lack of mutations in the p53 coding region of hyperproliferative alphaB-/- cells. However, the reentry of hyperproliferative alphaB-/- cells into S phase and mitosis after DNA damage by gamma-irradiation were consistent with impaired p53 checkpoint function in these cells. The results demonstrate that expression of functionally impaired p53 is one of the factors that promote immortalization of lens epithelial cells derived from alphaB-/- mice. Fluorescence in situ hybridization using probes prepared from centromere-specific mouse P1 clones of chromosomes 1 and 9 demonstrated that the hyperproliferative alphaB-/- cells were 30% diploid and 70% tetraploid, whereas wild type cells were 83% diploid. Further evidence of genomic instability was obtained when the hyperproliferative alphaB-/- cells were labeled with anti-beta-tubulin antibodies. Examination of the hyperproliferative alphaB-/- mitotic profiles revealed the presence of cells that failed to round up for mitosis, or arrested in cytokinesis, and binucleated cells in which nuclear division had occurred without cell division. These results suggest that the stress protein and molecular chaperone alphaB-crystallin protects cells from acquiring impaired p53 protein and genomic instability.  相似文献   
46.
47.
高粱舟蛾发生规律与防治研究   总被引:1,自引:0,他引:1  
高粱舟蛾Dinaracombusta (Walker)以幼虫取食玉米、高粱、甘蔗叶片。近年来 ,河北省正定、磁县、滦城等地危害夏玉米成灾。该虫在河北中南部每年发生 1代 ,以蛹在土中越冬 ,6月底至 7月上旬夏玉米田开始见卵 ,7月中下至 8月上旬为幼虫发生危害盛期。虫口密度与气象、天敌及食物因素有关。幼虫抗药性低 ,在夏玉米田采用高效氯氰菊酯乳油等低龄期防治 ,效果均在 90 %以上  相似文献   
48.

Background

Hypoxia-inducible factor 1α (HIF-1α) is an important regulator of immune and inflammatory responses. We hypothesized that nasal allergic inflammation is attenuated by HIF-1α inhibition and strengthened by HIF-1α stabilization.

Objective

To elucidate the role of HIF-1α in a murine model of allergic rhinitis (AR).

Methods

Mice were pretreated with the HIF-1α inhibitor 2-methoxyestradiol (2ME2) or the HIF-1α inducer cobalt chloride (CoCl2) in an established AR murine model using ovalbumin (OVA)-sensitized BALB/c mice. HIF-1α and vascular endothelial growth factor (VEGF) expression in nasal mucosa was measured and multiple parameters of allergic responses were evaluated.

Results

HIF-1α and VEGF levels were locally up-regulated in nasal mucosa during AR. Inflammatory responses to OVA challenge, including nasal symptoms, inflammatory cell infiltration, eosinophil recruitment, up-regulation of T-helper type 2 cytokines in nasal lavage fluid, and serum OVA-specific IgE levels were present in the OVA-challenged mice. 2ME2 effectively inhibited HIF-1α and VEGF expression and attenuated the inflammatory responses. Stabilization of HIF-1α by CoCl2 facilitated nasal allergic inflammation. HIF-1α protein levels in nasal airways correlated with the severity of AR in mice.

Conclusions

HIF-1α is intimately involved in the pathogenesis of nasal allergies, and the inhibition of HIF-1α may be useful as a novel therapeutic approach for AR.  相似文献   
49.
脂肪酶在微乳液和微乳液凝胶中催化辛酸辛醇的酯化反应   总被引:4,自引:0,他引:4  
脂肪酶在合成反应中具有很高的区域选择性和立体选择性 ,已广泛用于食品工业和药物工业[1,2 ] ,在有机介质中的脂肪酶催化反应已有较多研究[3 ,4 ] 。微乳液一般由表面活性剂、助表面活性剂、油和水等组份组成 ,它是一种热力学稳定、光学透明、宏观均匀而微观不均匀的体系 ,能提供酶催化所需要的巨大油 /水界面[5] 。而将脂肪酶增溶于油包水(W /O)微乳液中的纳米级“水池”中 ,可使酶以分子水平分散[6] ,图 1(a) ,从而可用来模拟细胞微环境中的反应。油包水微乳液中的酶可通过加入明胶而制成固定化酶 ,含明胶的微乳液凝胶 (MBGs)最早…  相似文献   
50.
“Song Lan” is a source of Chinese drugs such as “Daqingye”, “Banlangen” or “Qingdai”. We have discovered that the two species, “Song Lan” (Isatis indigotica Fort.) and woad (I. tinctoria L.), were mistakenly described in the literature due to their morphological polymorphism. In order to clarify the two species, cytology examination, pollen analysis, electrophoretic analysis of isoenzymes and soluble protein were performed. The results show that previous non-trichiferous type of woad is a “Song Lan”. As in woad, “Song Lan” is also morphologically of great variability. The base of canline leaves in this species may be sagittate or auriculate. We have not found the non-trichiferous type of woad in our country. It is reported for the first time that the chromosome number for “Song Lan” is 2n=14. The content of the indole glucoside in fresh leaves of “Song Lan” is about five timeshigher than in woad. For medicine cultivation of “Song Lan” is favorable.  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