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   8655篇
  免费   876篇
  国内免费   1104篇
  2024年   33篇
  2023年   136篇
  2022年   260篇
  2021年   497篇
  2020年   410篇
  2019年   465篇
  2018年   397篇
  2017年   311篇
  2016年   417篇
  2015年   605篇
  2014年   663篇
  2013年   684篇
  2012年   750篇
  2011年   714篇
  2010年   476篇
  2009年   380篇
  2008年   467篇
  2007年   460篇
  2006年   392篇
  2005年   318篇
  2004年   297篇
  2003年   263篇
  2002年   275篇
  2001年   157篇
  2000年   121篇
  1999年   112篇
  1998年   101篇
  1997年   62篇
  1996年   49篇
  1995年   37篇
  1994年   34篇
  1993年   38篇
  1992年   39篇
  1991年   27篇
  1990年   20篇
  1989年   26篇
  1988年   21篇
  1987年   16篇
  1986年   15篇
  1985年   12篇
  1984年   9篇
  1983年   9篇
  1982年   7篇
  1981年   7篇
  1980年   4篇
  1979年   8篇
  1978年   5篇
  1974年   5篇
  1970年   4篇
  1968年   4篇
排序方式: 共有10000条查询结果,搜索用时 281 毫秒
251.
本文对中国首例输入性D8基因型麻疹病毒基因特征进行分析。用ELISA法检测血清麻疹病毒IgM抗体;用Vero/Slam细胞对采集的咽拭子标本进行病毒分离,分离到的麻疹毒株用RT-PCR方法扩增其核蛋白基因3′端的部分序列,并对扩增产物进行核苷酸序列测定和分析,以3′端456个核苷酸为目的片段进行基因亲缘性关系分析。结果表明,上海市2012年共报告1 105疑似麻疹病例,其中实验室确诊590例,临床符合病例2例,排除513例,报告发病率为2.52/10万;共采集到984份疑似麻疹病例咽拭子标本,分离到247株麻疹病毒,病毒分离阳性率为25.3%;除Shanghai12-239为D8基因型外,其他均为H1a基因亚型。Shanghai12-239与世界卫生组织(World Health Organization,WHO)参考株(Manchester.UNK30.94(D8)AF280803)核苷酸序列同源性为97.8%,氨基酸序列同源性为98.6%。与WHO其他基因型参考株核苷酸序列同源性为89.6%~94.5%,氨基酸序列同源性为88.7%~95.3%。  相似文献   
252.
目的探讨内质网应激在高脂饮食引起的ApoE基因敲除小鼠附睾损伤中的作用及褪黑素(MT)的干预机制。方法将12只ApoE基因敲除的C57BL/6J雄性小鼠随机分为高脂饮食组及MT处理组。高脂饮食组为ApoE基因敲除小鼠,给予高脂饮食;MT处理组给予高脂饲养外,并MT灌胃。以6只野生型C57BL/6J雄性小鼠作为对照组,给予普通饮食。饲养12w后,取附睾组织制片,HE染色观察附睾的病理学形态,免疫组化检测GRP78和CHOP的表达。结果HE染色显示,高脂饮食组小鼠,附睾上皮细胞形态结构不清,细胞萎缩。对照组和褪黑素处理组小鼠附睾上皮细胞形态结构完整,细胞排列整齐。免疫组化显示高脂饮食组小鼠附睾中GRP78、CHOP表达增强(P〈0.01)。MT处理组和高脂饮食组相比,附睾中GRP78、CHOP表达下调(P〈0.01)。结论内质网应激参与高脂饮食导致的附睾损伤;MT可能通过抑制附睾内质网应激,减轻高脂饮食对小鼠附睾的损伤。  相似文献   
253.
The purpose of this study was to investigate the effect of repeated harvesting on the content of caffeic acid (CA) and seven species of caffeoylquinic acids (CQAs) in sweet potato leaves using a newly developed high-performance liquid chromatography method. Six cultivars and two breeding lines were used in this study. Leaves were collected at monthly intervals from 1st harvest (May) to 4th harvest (August) in 2011 and 2012. ANOVA analysis revealed that the contents of CQAs were significantly different among all cultivars and breeding lines, but no significant differences were found for CA. No annual variation was confirmed in CA and CQAs. Repeated harvest of sweet potato leaves affected the content of only 4-CQA and 5-CQA. Post-hoc comparisons using Tukey’s method indicated that the contents of 4-CQA and 5-CQA in sweet potato leaves harvested at first time were significantly higher compared to those at the other harvest times.  相似文献   
254.
通过比较4种小鼠粪便细菌总DNA提取方法对基于PCR-DGGE检测的肠道菌群多样性分析的影响,旨在建立适于PCR—DGGE的小鼠肠道微生物宏基因组提取的稳定、经济、快捷的方法。采用SDS裂解法、某国产市售粪便DNA提取试剂盒、改进的化学裂解法、改进的溶菌酶法4种方法提取小鼠粪便细菌总DNA,通过琼脂糖凝胶电泳、紫外分光光度法、细菌16S rRNAV3区PCR扩增结合DGGE对提取结果进行比较分析。SDS裂解法和国产市售试剂盒2种方法提取粪便细菌总DNA均未得到理想结果,另2种方法均能够检测到粪便中20种左右的细菌。改进的化学裂解法和改进的溶菌酶提取法的建立为基于PCR—DGGE进行肠道菌群结构的定量及定性分析提供了可靠的前提基础和实验保障。  相似文献   
255.
Highlights? PP2Ac is constitutively activated and targets MyD88 in LPS-tolerized macrophages ? Constitutively active PP2Ac shifts a proinflammatory MyD88 to its prosurvival mode ? Constitutively active PP2Ac reprograms gene-specific chromatin modification landscape ? Constitutively active PP2Ac broadly defines ET at both signaling and epigenetic levels  相似文献   
256.
257.
A new species of the genus Protobothrops Hoge Romano-Hoge, 1983, was described from Jilong County, southern Tibet, China, and Chungthang, northern Sikkim, India. It differs from congeners by the following characters: 1) relatively large body size(total length up to 1510 mm); 2) dorsal scale rows 25–25–19; 3) except for the smooth outermost row, dorsal scales are weakly keeled; 4) relatively high number of ventral(198–216) and subcaudal(65–76 pairs) scales; 5) 7–8 supralabials; 6) 11 to 13 infralabials; 7) dorsal head uniform dark brown, laterally a reddish-brown obscure postocular streak; 8) dorsum of trunk and tail olive, with distinct black edged red brown transverse bands across the body and tail; and 9) eye from bright brown and reddish brown to mildly brown. The new species was also observed from the Haa Valley in western Bhutan.  相似文献   
258.

Background

Infantile hemangioma (IH) is a benign vascular neoplasm that arises from the abnormal proliferation of endothelial cells and enhanced angiogenesis. Recently, propranolol has been found to be effective in the management of IH, suggesting that β-adrenergic receptors (β-ARs) may play an important role in the pathogenesis of IH.

Results

In the present study, we investigated the β-adrenergic signaling that is associated with hemangioma-derived endothelial cell (HemEC) proliferation. The results showed that both β1- and β2-ARs were expressed in HemECs. Stimulation of the β-ARs by isoprenaline induced cell proliferation and elevation of second messenger cAMP levels. The proliferation-promoting action of isoprenaline was abolished by a β1-selective antagonist and was more effectively abolished by a β2-selective antagonist; the mechanism for the action of the antagonists was a G0/G1 phase cell cycle arrest which was associated with decreased cyclin D1, CDK-4, CDK-6 and phospho-Rb expression. Pre-treatment of the cells with VEGFR-2 or ERK inhibitors also prevented the isoprenaline-mediated proliferation of cells. In agreement with the involvement of β-ARs and VEGFR-2 in the HemEC response, β-AR antagonists and the VEGFR-2 inhibitor significantly attenuated isoprenaline-induced ERK phosphorylation. Moreover, treating the cells with isoprenaline markedly increased VEGF-A expression and VEGFR-2 activity in a β2-AR-dependent manner.

Conclusions

We have demonstrated that the activation of the β-ARs in the ERK pathway may be important mechanisms in promoting HemEC growth. Furthermore, stimulation of the β-AR may transactivate VEGFR-2 signaling and further increase HemEC proliferation.  相似文献   
259.
The site-specific characterization of N-glycans in glycopro- teins with the potential of clinical application is important. In our previous report, the overall N-glycans of sera haptoglobin (Hp) β chain were found to be different in liver diseases. Hp β chain contains four potential sites of N-glycosylation. In this study, we investigated the potential change of N-glycans on Hp β chain in a site-specific fashion. Sera Hp β chain in healthy individuals as well as patients with hepatitis B virus (HBV), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) were purified, digested and subjected to liquid chromatography-electro- spray ionization-higher energy collision dissociation mass spectrometry, which allowed identification and structure determination of the glycopeptide, as well as the relative quantification of glycans present on each glycopeptide. The quantitative results revealed that the sialylation of NLFLN207HSEN211 ATAK and the fucosylated structure at all glycopeptides increased significantly in LC and HCC patients compared with those in HBV patients and healthy individuals. A set of different N-glycan patterns of Hp β chain in various liver diseases has been determined. Thus, the sialylated and fucosylated glycoforms of Hp β chain might be related to early hepatocarcinogenesis and also might be useful as novel differential markers for LC and HCC patients.  相似文献   
260.

Background

The pro-inflammatory status of the elderly triggers most of the age-related diseases such as cancer and atherosclerosis. Atherosclerosis, the leading cause world wide of morbidity and death, is an inflammatory disease influenced by life-style and genetic host factors. Stimuli such as oxLDL or microbial ligands have been proposed to trigger inflammation leading to atherosclerosis. It has recently been shown that oxLDL activates immune cells via the Toll-like receptor (TLR) 4/6 complex. Several common single nucleotide polymorphisms (SNPs) of the TLR system have been associated with atherosclerosis. To investigate the role of TLR-6 we analyzed the association of the TLR-6 SNP Pro249Ser with atherogenesis.

Results

Genotyping of two independent groups with CAD, as well as of healthy controls revealed a significant association of the homozygous genotype with a reduced risk for atherosclerosis (odds ratio: 0.69, 95% CI 0.51-0.95, P?=?0.02). In addition, we found a trend towards an association with the risk of restenosis after transluminal coronary angioplasty (odds ratio: 0.53, 95% CI 0.24-1.16, P?=?0.12). In addition, first evidence is presented that the frequency of this protective genotype increases in a healthy population with age. Taken together, our results define a role for TLR-6 and its genetic variations in modulating the inflammatory response leading to atherosclerosis.

Conclusions

These results may lead to a better risk stratification, and potentially to an improved prophylactic treatment of high-risk populations. Furthermore, the protective effect of this polymorphism may lead to an increase of this genotype in the healthy elderly and may therefore be a novel genetic marker for the well-being during aging.
  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