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排序方式: 共有998条查询结果,搜索用时 15 毫秒
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Spatial whole transcriptome profiling of primary tumor from patients with metastatic prostate cancer
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目的 基于网络药理学方法探讨补中益气汤治疗糖尿病胃轻瘫(Diabetic gastroparesis,DGP)的作用机制。方法 利用中药系统药理学成分分析平台(BATMAN-TCM)数据库获取补中益气汤的活性成分和作用靶点。从GEO数据库、DisGeNET数据库、GenCLiP 3数据库、GeneCards数据库以及TTD数据库收集DGP相关基因。将补中益气汤作用靶点和DGP相关基因取交集,得到补中益气汤治疗DGP的潜在靶点。利用Cytoscape3.7.1 软件构建中药活性成分-DGP靶点网络。运用STRING数据库分析交集基因所编码蛋白之间的相互作用,利用Cytoscape3.7.1 软件对结果进行可视化。利用Cytoscape软件中的ClueGO插件、CluePedia插件分别对交集靶点基因进行GO富集分析、KEGG通路富集分析及可视化。结果 筛选得到补中益气汤的185个活性成分,作用于130个DGP靶点基因,其中关键靶点10个,包括INS、AKT1、IL6、NOS3 和 AR等。GO功能和KEGG通路富集分析显示,补中益气汤可能通过抑制凋亡、自噬、氧化应激、炎症反应,调节胰岛素、血糖水平,改善胃肠道平滑肌细胞和ICC损伤,以影响DGP的发生发展。结论 本研究初步揭示了补中益气汤通过多成分-多靶点-多通路治疗DGP的作用机制,为后续更加深入研究补中益气汤的药效和作用机制提供研究方向和理论依据。 相似文献
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《Saudi Pharmaceutical Journal》2022,30(12):1736-1747
Cystic fibrosis (CF) is a genetic disease that affects the exocrine glands and is caused by cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations. Lung disease is the leading cause of morbidity in patients. Target-specific treatment of CF has been achieved using monoclonal antibodies (mAbs). The purpose of this article is to discuss the possibility of treating CF with mAbs through their significant target specificity. We searched electronic databases in Web of Science, PubMed, EMBASE, Scopus, and Google Scholar from 1984 to 2021. We discussed the critical role of targeted therapy in cystic fibrosis, as it will be more effective at suppressing the molecular networks. After conducting a critical review of the available literature, we concluded that it is critical to understand the fundamental molecular mechanisms underlying CF prior to incorporating biologics into the therapy regimen. Omalizumab, Mepolizumab, Benralizumab, Dupilumab and KB001-A have been successfully screened for asthma-complicated CF, and their efficacies have been well reported. Despite the availability of effective targeted biologics, treating CF has remained a difficult task, particularly when it comes to reduction of secondary inflammatory mediators. This review emphasizes the overall views on CF, the immunological mechanism of CF, and the prospective therapeutic use of mAbs as potential targeted biologics for enhancing the overall status of human health. 相似文献
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缺血性脑卒中(cerebral ischemic stroke,CIS)可引发包括心、肝、脾、肺、肾在内的多个器官损伤,该类疾病是由多个病理环节组成,具有复杂的发病机制及高发病率、高致残率和高死亡率的特点,严重者可形成多器官功能障碍综合征(multiple organ dysfunction syndromes,MODS)。目前任何针对单一环节、单一靶点的治疗都不足以应对这一问题。研究发现中药可经多途径、多靶点,参与疾病的多个环节干预疾病。中药通过抗氧化作用、抑制炎症反应、调节能量代谢等对CIS引发的多器官损伤具有明显的保护作用。对中药及其有效成分对CIS后引起的多器官损伤及其相关机制进行了综述,以期更大程度地发挥祖国医学的治疗作用和治疗范围,为中药临床干预脑血管类合并多器官损伤类疾病提供科学依据和参考。 相似文献
6.
Hepatocellular carcinoma (HCC) is one of the most frequent and fatal human cancers worldwide and its development and prognosis are intimately associated with chronic infection with hepatitis B virus (HBV). The identification of genetic mutations and molecular mechanisms that mediate HBV-induced tumorigenesis therefore holds promise for the development of potential biomarkers and targets for HCC prevention and therapy. The presence of HBV pre-S gene deletions in the blood and the expression of pre-S deleted proteins in the liver tissues of patients with chronic hepatitis B and HBV-related HCC have emerged as valuable biomarkers for higher incidence rates of HCC development and a higher risk of HCC recurrence after curative surgical resection, respectively. Moreover, pre-S deleted proteins are regarded as important oncoproteins that activate multiple signaling pathways to induce DNA damage and promote growth and proliferation in hepatocytes, leading to HCC development. The signaling molecules dysregulated by pre-S deleted proteins have also been validated as potential targets for the prevention of HCC development. In this review, we summarize the clinical and molecular implications of HBV pre-S gene deletions and pre-S deleted proteins in HCC development and recurrence and highlight their potential applications in HCC prevention and therapy. 相似文献
7.
Alfred K. Cheung Tara I. Chang William C. Cushman Susan L. Furth Fan Fan Hou Joachim H. Ix Gregory A. Knoll Paul Muntner Roberto Pecoits-Filho Mark J. Sarnak Sheldon W. Tobe Charles R.V. Tomson Lyubov Lytvyn Jonathan C. Craig David J. Tunnicliffe Martin Howell Marcello Tonelli Michael Cheung Johannes F.E. Mann 《Kidney international》2021,99(3):559-569
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目的:基于网络药理学分析土鳖虫对破血逐瘀相关疾病的作用机制。方法:经文献查阅并结合PubChem、SwissADME、SwissTargetPrediction和TCMSP等数据库对土鳖虫已知成分及其对应靶点进行搜集,并与经GeneCards、OMIM、TTD、HPO数据库搜索得到的“破血逐瘀”相关靶点进行交互分析得到共同靶点;通过蛋白-蛋白质-蛋白质相互作用(PPI)分析、基因本体(GO)分析和京都基因与基因组百科全书(KEGG)分析,构建土鳖虫“成分-靶点-疾病”网络,探讨土鳖虫破血逐瘀功效的作用机制。同时采用体外纤溶实验评价土鳖虫水溶性蛋白质与其他成分的活性差异。结果:筛选得到土鳖虫活性化合物54个,共对应靶点653个;与血瘀相关的17种疾病的16141个作用靶点经交互分析得出两者共有靶点26个。GO和KEGG分析结果表明,土鳖虫已知成分主要涉及嘌呤代谢通路、细胞能量代谢通路、环磷酸鸟苷(cGMP)信号通路、Toll样受体信号通路、醛固酮合成代谢通路、三酰甘油合成通路等13条信号通路,通过干预DNA转录、细胞能量代谢等生物功能发挥药效。同时体外纤溶实验得出土鳖虫水溶性蛋白质较其他成分表现出更强的纤溶活性。结论:土鳖虫已知活性成分并不能很好的证明其对破血逐瘀相关疾病的治疗有显著的效果。结合土鳖虫水溶性蛋白质促纤溶作用,为下一步土鳖虫纤溶物质基础的研究提供参考。 相似文献
9.
目的 基于网络药理学研究栝楼桂枝汤治疗脑卒中后下肢痉挛的作用机制。方法 利用TCMSP数据库、SwissTarget Prediction数据平台筛选栝楼桂枝汤活性成分靶点,并借助Gephi软件构建活性成分-靶点网络,运用Genecard、DisGeNET、TTD疾病数据库筛选作用于脑卒中、下肢痉挛靶基因,应用STRING平台构建靶蛋白相互作用网络,利用ClueGO软件对靶基因进行GO功能分析,通过DAVID v6.8平台对关键靶点KEGG通路进行分析。结果 栝楼桂枝汤中黄酮类、有机酸类、皂苷类等成分作用于IL6、TNF、EGFR、ESR1、TP53、STAT3、F2等49个关键靶基因;参与横纹肌细胞增殖、骨重塑、平滑肌细胞增殖正调控、肌细胞增殖、内皮细胞增殖等14类生物过程;调控TNF、MAPK、PI3K-Akt、ALS、神经营养、5-羟色胺能神经突触等30条信号通路。结论 栝楼桂枝汤多种活性成分通过抗炎、抗氧化、神经营养及保护等药理作用,以及参与肌细胞增殖等生物过程,从中枢神经系统及外周肌肉组织双向治疗脑卒中后下肢痉挛。 相似文献
10.
Choroidal neovascularization characterizes wet age-related macular degeneration. Choroidal neovascularization formation involves a primarily angiogenic process that is combined with both inflammation and proteolysis. A primary cause of choroidal neovascularization pathogenesis is alterations in pro-and anti-angiogenic factors derived from the retinal pigment epithelium, with vascular endothelium growth factor being mainly responsible for both clinical and experimental choroidal neovascularization. MicroRNAs(miRNAs) which are short, non-coding, endogenous RNA molecules have a major role in regulating various pathological processes, including inflammation and angiogenesis. A review of recent studies with the mouse laser-induced choroidal neovascularization model has shown alterations in miRNA expression in choroidal neovascularization tissues and could be potential therapeutic targets for wet age-related macular degeneration. Upregulation of miR-505(days 1 and 3 post-laser), miR-155(day 14) occurred in retina; miR-342-5 p(days 3 and 7), miR-126-3 p(day 14) in choroid; miR-23 a, miR-24, miR-27 a(day 7) in retina/choroid; miR-505(days 1 and 3) in retinal pigment epithelium/choroid; downregulation of miR-155(days 1 and 3), miR-29 a, miR-29 b, miR-29 c(day 5), miR-93(day 14), miR-126(day 14) occurred in retinal pigment epithelium/choroid. Therapies using miRNA mimics or inhibitors were found to decrease choroidal neovascularization lesions. Choroidal neovascularization development was reduced by overexpression of miR-155, miR-188-5 p, miR-(5,B,7), miR-126-3 p, miR-342-5 p, miR-93, miR-126, miR-195 a-3 p, miR-24, miR-21, miR-31, miR-150, and miR-184, or suppression of miR-505, miR-126-3 p, miR-155, and miR-23/27. Further studies are warranted to determine miRNA expression in mouse laser-induced choroidal neovascularization models in order to validate and extend the reported findings. Important experimental variables need to be standardized; these include the strain and age of animals, gender, number and position of laser burns to the eye, laser parameters to induce choroidal neovascularization lesions including wavelength, power, spot size, and duration. 相似文献