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   18946篇
  免费   1379篇
  国内免费   1236篇
  21561篇
  2024年   41篇
  2023年   254篇
  2022年   537篇
  2021年   922篇
  2020年   563篇
  2019年   804篇
  2018年   797篇
  2017年   561篇
  2016年   831篇
  2015年   1101篇
  2014年   1345篇
  2013年   1442篇
  2012年   1673篇
  2011年   1520篇
  2010年   968篇
  2009年   935篇
  2008年   1043篇
  2007年   976篇
  2006年   797篇
  2005年   682篇
  2004年   530篇
  2003年   518篇
  2002年   437篇
  2001年   344篇
  2000年   300篇
  1999年   289篇
  1998年   164篇
  1997年   158篇
  1996年   155篇
  1995年   117篇
  1994年   84篇
  1993年   70篇
  1992年   110篇
  1991年   82篇
  1990年   68篇
  1989年   52篇
  1988年   43篇
  1987年   43篇
  1986年   38篇
  1985年   51篇
  1984年   8篇
  1983年   17篇
  1982年   9篇
  1981年   11篇
  1980年   7篇
  1979年   7篇
  1978年   6篇
  1977年   5篇
  1974年   5篇
  1969年   11篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
231.
乙型肝炎病毒感染引起的慢性乙型肝炎(Chronic hepatitis B,CHB)是一种全球性流行疾病,严重时可引起肝功能衰竭,甚至发展成肝硬化和肝癌.也已发现CHB的发生和发展与肠道菌群的组成和结构的变化密切相关.为进一步探究肠道菌群结构与肝脏生化指标之间的联系,文中随机纳入14名CHB患者和11名健康对照者(Co...  相似文献   
232.
Melatonin has been reported to have tumor-suppressive effects via comprehensive molecular mechanisms, and long non-coding RNAs (lncRNAs) may participate in this process. However, the mechanism by which melatonin affects the function of lncRNAs in triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is still unknown. Therefore, we aimed to investigate the differentially expressed mRNAs and lncRNAs in melatonin-treated TNBC cells and the interaction mechanisms. Microarray analyses were performed to identify differentially expressed mRNAs and lncRNAs in TNBC cell lines after melatonin treatment. To explore the functions and underlying mechanisms of the mRNAs and lncRNAs candidates, a series of in vitro experiments were conducted, including CCK-8, Transwell, colony formation, luciferase reporter gene, and RNA immunoprecipitation (RIP) assays, and mouse xenograft models were established. We found that after melatonin treatment, FUNDC1 and lnc049808 downregulated in TNBC cell lines. Knockdown of FUNDC1 and lnc049808 inhibited TNBC cell proliferation, invasion, and metastasis. Moreover, lnc049808 and FUNDC1 acted as competing endogenous RNAs (ceRNAs) for binding to miR-101. These findings indicated that melatonin inhibited TNBC progression through the lnc049808-FUNDC1 pathway and melatonin could be used as a potential therapeutic agent for TNBC.Subject terms: Breast cancer, Non-coding RNAs  相似文献   
233.
Research on species richness patterns and the advanced elevational Rapoport rule (ERR) has been widespread in recent years; however, there is a lack of such research for the temperate mountainous regions in northeast Asia. Here, we collected plant species from the Seorak Mountain in northeast Asia through field surveys. The species were divided into 11 groups according to the life‐form types and phytogeography affinities of each species. The ERR was evaluated using Steven''s method and by examining the species richness patterns of each group. The species richness patterns revealed a positive multimodal pattern along the elevation gradient, but phytogeography affinities (increasing trend) and life‐form analysis (unimodal) exhibited different patterns. The elevation gradients (1,350 m for the mean elevation–range relationships), which are affected by the boundary effect and different life forms, did not consistently support the ERR. However, herbs as well as rare, endemic, and red list species showed consistent support for the ERR, which could be attributed to the influence by phytogeography affinities. Therefore, the results from Seorak Mountain showed that the ERR was not consistent for different plant life forms in the same area; however, phytogeography affinities could support and explain ERR.  相似文献   
234.
The Pleistocene climatic oscillations had profound effects on the demographic history and genetic diversification of plants in arid north-west China where some glacial refugia have been recognized. The genus Ixiolirion comprises three species, of which two, I. tataricum and I. songaricum (endemic), occur in China. In some locations they are sympatric. We investigated their population structure and population history in response to past climatic change using a sample of 619 individuals in 34 populations with nITS and ptDNA sequences. A significant genetic divergence between the two species was supported by a high level of pairwise genetic differentiation, very low gene flow, and phylogenetic analysis showing that I. songaricum haplotypes were monophyletic, whereas those of I. tataricum were polyphyletic. We found significant differentiation and phylogeographic structure in both species. The split of the two species was dated to the late Miocene (~7?Ma), but deep divergence occurred in the mid-late Quaternary. A similar haplotype distribution pattern was found in both species: one to two dominant haplotypes across most populations, with unique haplotypes in a few populations or a geographic group. The genetic diversity, haplotype number, and haplotype diversity decreased from the Yili Valley to the central Tianshan and Barluk Mountains. Additionally, ptDNA analysis showed that I. tataricum diversified in the eastern Tianshan and Barluk Mountains, which might be due to physical barriers to long distance seed dispersal such as desert. In conclusion, our results indicated that the Yili Valley was likely a glacial refuge for Ixiolirion in China, with postglacial dispersal from the Yili Valley eastward to the eastern Tianshan Mountains, and northward to the Barluk Mountains. The climatic changes in the Miocene and Pleistocene and geographic barriers are important factors driving species divergence and differentiation of Ixiolirion and other taxa.  相似文献   
235.
Hirschsprung disease (HSCR) is a congenital disorder characterized by aganglionosis of the distal intestine. To assess the contribution of copy number variants (CNVs) to HSCR, we analysed the data generated from our previous genome-wide association study on HSCR patients, whereby we identified NRG1 as a new HSCR susceptibility locus. Analysis of 129 Chinese patients and 331 ethnically matched controls showed that HSCR patients have a greater burden of rare CNVs (p = 1.50 × 10(-5)), particularly for those encompassing genes (p = 5.00 × 10(-6)). Our study identified 246 rare-genic CNVs exclusive to patients. Among those, we detected a NRG3 deletion (p = 1.64 × 10(-3)). Subsequent follow-up (96 additional patients and 220 controls) on NRG3 revealed 9 deletions (combined p = 3.36 × 10(-5)) and 2 de novo duplications among patients and two deletions among controls. Importantly, NRG3 is a paralog of NRG1. Stratification of patients by presence/absence of HSCR-associated syndromes showed that while syndromic-HSCR patients carried significantly longer CNVs than the non-syndromic or controls (p = 1.50 × 10(-5)), non-syndromic patients were enriched in CNV number when compared to controls (p = 4.00 × 10(-6)) or the syndromic counterpart. Our results suggest a role for NRG3 in HSCR etiology and provide insights into the relative contribution of structural variants in both syndromic and non-syndromic HSCR. This would be the first genome-wide catalog of copy number variants identified in HSCR.  相似文献   
236.
Y Zhu  W Hua  M Xu  W He  X Wang  Y Dai  S Zhao  J Tang  S Wang  S Lu 《PloS one》2012,7(8):e44032

Background

Schistosomiasis japonica remains a real threat to public health in China. The currently used immunodiagnostic assays are sensitive and have a certain degree of specificity, however, they all use complex crude antigens, are based on detection of schistosome-specific antibodies, and have been shown to cross-react with other parasitic diseases. Therefore, these assays cannot be used to evaluate chemotherapy efficacy. The development of highly sensitive and highly specific immunodiagnostic techniques that can monitor the decline of antibodies specific for S. japonica will be extremely valuable as part of the ongoing strategy to control schistosomiasis in endemic areas. Here we report on the identification of unique fraction antigens of soluble egg antigen (SEA) to which the antibodies disappear 7 weeks after effective treatment. Furthermore, we use these SEA fractions to develop a modified assay with both high sensitivity and specificity.

Methodology/Principal Findings

SEA of S. japonicum was fractionated by electrophoresis using 7.5% SDS-PAGE under non-reducing conditions. The SEA fraction antigens to which antibodies were decreased soon after treatment were collected and used as the detection antigens to establish the FA-ELISA. Sera from patients with acute and chronic schistosomiasis infection, healthy people, and those with other parasitic diseases, were used to evaluate their sensitivity and specificity. Furthermore, sera from patients with chronic schistosomiasis infection were evaluated before and after treatment at different time points to evaluate their chemotherapeutic efficacy.

Conclusion/Significance

We demonstrated that this novel FA-ELISA provided high sensitivity and specificity, with very low cross-reactivity, and can serve as an effective tool to determine the efficacy of chemotherapy against S. japonicum.  相似文献   
237.
Chronic lung infection by mucoid Pseudomonas aeruginosa is one of the major pathologic features in patients with cystic fibrosis. Mucoid P.?aeruginosa is notorious for its biofilm forming capability and resistance to immune attacks. In this study, the roles of extracellular polymeric substances from biofilms formed by mucoid P.?aeruginosa were investigated. Alginate is not an essential structure component for mucoid P.?aeruginosa biofilms. Genetic studies revealed that Pel and Psl polysaccharides serve as essential scaffold and mediate macrocolony formation in mucoid P.?aeruginosa biofilms. The Psl polysaccharide is more important than Pel polysaccharide in mucoid P.?aeruginosa biofilm structure maintenance and phagocytosis resistance. The polysaccharides were further found to protect mucoid P.?aeruginosa strain from host immune clearance in a mouse model of acute lung infection.  相似文献   
238.
Song Y  Du B  Zhou T  Han B  Yu F  Yang R  Hu X  Ni Y  Li Q 《Carbohydrate research》2011,(2):958-310
In this work, response surface methodology was used to determine optimum conditions for extraction of polysaccharides from defatted peanut cake. A central composite design including independent variables, such as extraction temperature (x1), extraction time (x2), and ethanol concentration (x3) was used. Selected response which evaluates the extraction process was polysaccharide yield, and the second-order model obtained for polysaccharide yield revealed coefficient of determination of 97.81%. The independent variable with the largest effect on response was ethanol concentration (x3). The optimum extraction conditions were found to be extraction temperature 48.7 °C, extraction time 1.52 h, and ethanol concentration of 61.9% (v/v), respectively. Under these conditions, the extraction efficiency of polysaccharide can increase to 25.89%. The results of structural analysis showed that the main composition of defatted peanut cake polysaccharide was α-galactose.  相似文献   
239.
落叶松人工林土壤热传导季节变化及其与环境因子的关系   总被引:2,自引:0,他引:2  
以2003—2005年落叶松人工林土壤热状况的实际监测数据为基础,研究了其土壤热传导特性及其与环境因子的关系.结果表明:落叶松人工林不同年份、不同地点土壤热通量的季节变化十分明显,4—8月为正值,9月至次年3月的绝大部分时间为负值,其年收支基本处于平衡状态.土壤热通量和土壤热导率(k)受净辐射影响显著,并存在时间延迟效应,冬季为4~5 h,夏季为2~3 h.基于实测的土壤热通量和土壤温度差计算得到的k值早春季节显著高于其他季节(P<0.05),而其他月份不存在显著差异(P>0.05).使用我国大多数气象观测站积累的土壤温差数据和 k值进行土壤热通量季节变化估计时,早春季节(3—5月)可能会产生较大的误差.  相似文献   
240.
Kim MN  Kim N  Lee SH  Park YS  Hwang JH  Kim JW  Jeong SH  Lee DH  Kim JS  Jung HC  Song IS 《Helicobacter》2008,13(4):261-268
Background: This study was performed to evaluate whether the addition of probiotics to proton pump inhibitor (PPI)‐based triple therapy increases the likelihood of successful Helicobacter pylori eradication. Materials and Methods: Three hundred and forty‐seven H. pylori‐infected patients were randomized into a triple‐plus‐yogurt group (yogurt group, n = 168) or a triple‐only group (control group, n = 179). Triple therapy consisted of PPI b.i.d., clarithromycin 500 mg b.i.d., and amoxicillin 1 g b.i.d. for 7 days. Yogurt group received triple therapy for 1 week and one bottle of Will yogurt per day for at 3 weeks, starting on the first day of triple therapy. Will yogurt (a Korean brand) contains Lactobacillus acidophilus HY2177, Lactobacillus casei HY2743, Bifidobacterium longum HY8001, and Streptococcus thermophilus B‐1. 13C‐urea breath test was performed at least 4 weeks after completion of triple therapy. Eradication rates, compliances, and adverse events were compared. Results: By intention‐to treat analysis the H. pylori eradication rates in the yogurt group 79.2% (133 of 168) was similar to that in the control group 72.1% (129 of 179) (p = .124). However, by per‐protocol (PP) analysis, the eradication rate in the yogurt group, 87.5% (133 of 152) was higher than that in the control group, 78.7% (129 of 164) (p = .037). Common adverse events were metallic taste (11.8%) and diarrhea (8.6%). The frequency of adverse effects in the yogurt group 41.1% (69/168) were higher than in the control group, 26.3% (47 of 179) (p = .003). However, most adverse events were mild to moderate in intensity, and the severities of adverse effects were similar in both groups (p = .401). Conclusions: The addition of Will yogurt to triple therapy did not reduce the side‐effects of triple therapy. But it increased the H. pylori eradication rate by PP analysis, encouraging more research in this field.  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