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   31238篇
  免费   4034篇
  国内免费   1316篇
耳鼻咽喉   118篇
儿科学   709篇
妇产科学   377篇
基础医学   3688篇
口腔科学   602篇
临床医学   3156篇
内科学   5937篇
皮肤病学   341篇
神经病学   2154篇
特种医学   595篇
外国民族医学   6篇
外科学   2388篇
综合类   4365篇
现状与发展   8篇
一般理论   1篇
预防医学   2467篇
眼科学   428篇
药学   4407篇
  29篇
中国医学   2457篇
肿瘤学   2355篇
  2024年   239篇
  2023年   967篇
  2022年   2145篇
  2021年   2554篇
  2020年   1973篇
  2019年   1511篇
  2018年   1418篇
  2017年   1427篇
  2016年   1570篇
  2015年   1655篇
  2014年   2254篇
  2013年   2631篇
  2012年   2030篇
  2011年   2050篇
  2010年   1446篇
  2009年   1307篇
  2008年   1297篇
  2007年   1184篇
  2006年   873篇
  2005年   779篇
  2004年   556篇
  2003年   508篇
  2002年   429篇
  2001年   350篇
  2000年   269篇
  1999年   302篇
  1998年   228篇
  1997年   225篇
  1996年   218篇
  1995年   180篇
  1994年   175篇
  1993年   141篇
  1992年   156篇
  1991年   142篇
  1990年   110篇
  1989年   136篇
  1988年   99篇
  1987年   91篇
  1986年   111篇
  1985年   137篇
  1984年   127篇
  1983年   108篇
  1982年   113篇
  1981年   90篇
  1980年   72篇
  1979年   43篇
  1978年   43篇
  1977年   25篇
  1976年   21篇
  1973年   18篇
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
1.

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Methods

Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.

Results

Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).

Conclusions

Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF.  相似文献   
2.
INTRODUCTIONPsoriasis is a chronic inflammatory condition that affects the skin and joints, and is associated with cardiovascular risk factors, including metabolic syndrome (MetS). We aimed to assess the prevalence of MetS in patients with psoriasis and determine whether there was a correlation between psoriasis severity and MetS in a Singapore population.METHODSThis was a cross-sectional study of patients with psoriasis, aged 18–69 years, who attended a tertiary dermatology referral centre in Singapore from October 2007 to February 2009. Fasting glucose, lipids, blood pressure, Psoriasis Area and Severity Index, and body mass index were measured. MetS was diagnosed in the presence of three or more criteria of the modified National Cholesterol Education Program Adult Treatment Panel III.RESULTSAmong 338 patients with psoriasis, there were 238 (70.4%) men and 100 (29.6%) women, who were Chinese (n = 228; 67.5%), Malay (n = 52; 15.4%) and Indian (n = 58; 17.2%). The prevalence of MetS was 45.1%. MetS was 44% more prevalent in patients older than 50 years (p = 0.02). Malay patients with psoriasis were significantly more likely to have hypertriglyceridaemia, elevated fasting plasma glucose and abdominal obesity. There was no significant correlation between psoriasis severity and risk of MetS.CONCLUSIONThe prevalence of MetS in patients with psoriasis in Singapore was 45.1%, or nearly threefold higher than the Singapore general population. Patients with psoriasis should be screened yearly for MetS and any modifiable cardiovascular risk factors should be actively controlled.  相似文献   
3.
目的 收集藿香正气汤的主要活性成分,通过分子对接及网络药理学探讨其防控新型冠状病毒肺炎(COVID-19)的有效成分及治疗机制。方法 通过基于配体-蛋白质相互作用的计算方法,以瑞德西韦为对照,探索藿香正气汤潜在治疗COVID-19的成分,并选出对接较好成分进行药理学机制预测,初探其药理学机制。结果 本研究筛选出5种与新冠病毒3CLpro结合能力强于瑞德西韦的小分子成分。网络药理学初步预测抗病毒途径可能是通过PI3K-Akt 信号通路影响病毒复制。结论 成分C1-C5与3CLpro结合良好,推测其可能是潜在的3CLpro的抑制剂,为抗病毒天然药物的开发提供了理论依据。  相似文献   
4.
日间手术在国外已有上百年的发展历史,现已成为欧美国家重要手术模式。我国于20世纪初开始开展日间手术,但目前尚未普及,发展不平衡问题比较突出,存在认识不清、开展不规范、与医保支付对接不畅等问题。日间手术是一种使国家、医院和病人三方均受益的新型手术模式。近年来,国家相关管理部门积极引导,开展日间手术的医院明显增多,可以预见,我国日间手术即将进入快速发展的新阶段。因此,有条件的医院可以从简单、易操作的病种开始,落实临床路径,积累经验,再逐步稳妥展开。在保证质量的前提下,不断拓展日间手术范围,提高三、四级手术比例。同时,积极与医保支付政策对接,采取灵活的方式,获得医保的支持,更好地促进我国日间手术的快速发展。  相似文献   
5.
6.
Background: Dense deposit disease and atypical hemolytic uremic syndrome are often caused by Complement Factor H (CFH) mutations. This study describes the retinal abnormalities in dense deposit disease and, for the first time, atypical haemolytic uremic syndrome. It also reviews our understanding of drusen pathogenesis and their relevance for glomerular disease. Methods: Six individuals with dense deposit disease and one with atypical haemolytic uremic syndrome were studied from 2 to 40 years after presentation. Five had renal transplants. All four who had genetic testing had CFH mutations. Individuals underwent ophthalmological review and retinal photography, and in some cases, optical coherence tomography, and further tests of retinal function. Results: All subjects with dense deposit disease had impaired night vision and retinal drusen or whitish-yellow deposits. Retinal atrophy, pigmentation, and hemorrhage were common. In late disease, peripheral vision was restricted, central vision was distorted, and there were scotoma from sub-retinal choroidal neovascular membranes and atypical serous retinopathy. Drusen were present but less prominent in the young person with atypical uremic syndrome due to a heterozygous CFH mutation. Conclusions: Drusen are common in forms of C3 glomerulopathy caused by compound heterozygous or heterozygous CFH mutations. They are useful diagnostically but also impair vision. Drusen have an identical composition to glomerular deposits. They are also identical to the drusen of age-related macular degeneration, and may respond to the same treatments. Individuals with a C3 glomerulopathy should be assessed ophthalmologically at diagnosis, and monitored regularly for vision-threatening complications.  相似文献   
7.
8.
1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.

2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.

3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A2/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.  相似文献   

9.
动脉粥样硬化是临床常见的冠心病和脑梗死等缺血性心脑血管疾病的主要病理基础,其病因复杂,发病机制尚未完全阐明。近年来,越来越多的研究显示鞘磷脂类信号通路可通过调节脂代谢、炎症和血管内皮功能等影响动脉粥样硬化的发生发展。文章综述了鞘磷脂类信号通路关键分子鞘磷脂、神经酰胺和1-磷酸鞘氨醇与动脉粥样硬化的关系,旨在为防治疾病提供新思路。  相似文献   
10.
Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus; however, the molecular mechanisms underlying DLE remain unknown. Therefore, we aimed to identify key differentially expressed genes (DEGs) in discoid lupus skin and investigate their potential pathways.To identify candidate genes involved in the occurrence and development of the disease, we downloaded the microarray datasets GSE52471 and GSE72535 from the Gene Expression Database (GEO). DEGs between discoid lupus skin and normal controls were selected using the GEO2R tool and Venn diagram software (http://bioinformatics.psb.ugent.be/webtools/Venn/). The Database for Annotation, Visualization, and Integrated Discovery (DAVID), Enrichr, and Cytoscape ClueGo were used to analyze the Kyoto Encyclopedia of Gene and Genome pathways and gene ontology. Protein-protein interactions (PPIs) of these DEGs were further assessed using the Search Tool for the Retrieval Interacting Genes version 10.0.Seventy three DEGs were co-expressed in both datasets. DEGs were predominantly upregulated in receptor signaling pathways of the immune response. In the PPI network, 69 upregulated genes were selected. Furthermore, 4 genes (CXCL10, ISG15, IFIH1, and IRF7) were found to be significantly upregulated in the RIG-I-like receptor signaling pathway, from analysis of Enrichr and Cytoscape ClueGo.The results of this study may provide new insights into the potential molecular mechanisms of DLE. However, further experimentation is required to confirm these findings.  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