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   4356篇
  免费   465篇
  国内免费   177篇
耳鼻咽喉   139篇
儿科学   130篇
妇产科学   191篇
基础医学   786篇
口腔科学   58篇
临床医学   348篇
内科学   665篇
皮肤病学   184篇
神经病学   175篇
特种医学   45篇
外科学   583篇
综合类   657篇
预防医学   331篇
眼科学   71篇
药学   162篇
中国医学   20篇
肿瘤学   453篇
  2024年   2篇
  2023年   19篇
  2022年   41篇
  2021年   79篇
  2020年   55篇
  2019年   64篇
  2018年   43篇
  2017年   71篇
  2016年   97篇
  2015年   78篇
  2014年   129篇
  2013年   184篇
  2012年   248篇
  2011年   273篇
  2010年   276篇
  2009年   324篇
  2008年   333篇
  2007年   403篇
  2006年   421篇
  2005年   320篇
  2004年   275篇
  2003年   275篇
  2002年   221篇
  2001年   205篇
  2000年   171篇
  1999年   109篇
  1998年   81篇
  1997年   73篇
  1996年   31篇
  1995年   34篇
  1994年   28篇
  1992年   1篇
  1991年   2篇
  1990年   4篇
  1989年   1篇
  1988年   4篇
  1987年   4篇
  1986年   6篇
  1985年   6篇
  1984年   1篇
  1982年   1篇
  1979年   2篇
  1977年   1篇
  1973年   1篇
  1967年   1篇
排序方式: 共有4998条查询结果,搜索用时 15 毫秒
1.
2.
目的通过生物信息学分析筛选脓毒症诱导急性肺损伤(ALI)的关键基因。 方法从基因表达谱(GEO)数据库中下载GSE10474数据集,该数据集包含13例脓毒症ALI患者样本(ALI组)和21例脓毒症患者样本(脓毒症组)基因数据。使用limma包筛选两组样本的差异表达基因,并对筛选出的差异表达基因进行基因本体论(GO)功能分析及京都基因与基因组百科全书(KEGG)富集分析。通过STRING数据库构建蛋白质相互作用(PPI)网络并确定前10位hub基因。 结果从GSE10474数据集中共筛选出115个差异表达基因,其中65个上调基因,50个下调基因。GO分析显示,生物过程的基因主要富集在金属离子稳态、氧化应激、电离辐射等;细胞组分主要富集在液泡膜、高尔基体膜、内质网膜、溶酶体膜等生物膜;这些基因主要与生物跨膜、泛素结合酶活性、蛋白络氨酸、丝氨酸和苏氨酸激酶结合蛋白活性以及蛋白激酶抑制活性等分子功能相关。KEGG富集分析显示,差异表达基因主要富集在磷脂酶信号通路、胰岛素信号通路、T细胞介导的免疫反应以及免疫相关的信号通路。PPI网络图筛选出了前10位hub基因,分别为CD4、CD74、髓细胞核分化抗原(MNDA)、髓细胞触发受体1(TREM1)、人白细胞抗原DRA(HLA-DRA)、细胞附着蛋白1相互作用蛋白(CYTIP)、凝血因子XⅢA链(F13A1)、血清胱抑素F(CST7)、丝裂原激活蛋白激酶1(MAPK1)、细胞周期蛋白依赖性激酶抑制剂1A(CDKN1A)。 结论CD4、CD74、MNDA、TREM1、HLA-DRA、CYTIP、F13A1、CST7、MAPK1及CDKN1A是脓毒症诱导ALI的关键基因,可作为临床治疗和新药开发的新靶点。  相似文献   
3.
子宫浆液性癌(uterine serous carcinoma,USC)是一种特殊类型的子宫内膜癌。有别于常见的子宫内膜样腺癌,USC较为少见,且恶性程度高,侵袭转移风险高,临床上预后较差。随着子宫内膜癌分子学研究的不断深入,分子学特征被应用于子宫内膜癌的病理分型诊断、治疗和预后评价中。研究发现USC中存在多种基因的突变,这些相关基因的突变对该病的诊断和预后具有重要的指导意义。同时,特异性的分子学改变为USC的靶向治疗提供了潜在的治疗靶点。目前,多种靶向治疗手段包括人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)抑制剂、免疫检查点抑制剂、抗血管生成治疗、磷脂酰肌醇3激酶(phosphoinositide 3-kinases,PI3K)通路抑制剂和多腺苷二磷酸核糖聚合酶[poly(ADP-ribose) polymerase,PARP]抑制剂等被应用于USC的临床治疗研究中,针对性的靶向治疗有望成为USC治疗的新突破。  相似文献   
4.
Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is the fourth commonest female malignancy worldwide. CESC progresses in immune-microenvironment mainly composed of infiltrating immune and stromal cells. Here, we performed an integrated analysis incorporating the expression profiles from the Cancer Genome Atlas (TCGA) database and scores of immune and stromal cells calculated by Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm. A two-gene signature (CD1C and CD6 genes) was established to predict the prognosis of CESC. Based on this signature, patients were divided into the high- and low-risk groups, and this signature showed good prognostic performance according to the results of Kaplan-Meier analysis and receiver operating characteristic (ROC) analysis in train set and two validation sets. A nomogram was built for evaluating the clinical applicability of this signature. In addition, based on Tumor Immune Estimation Resource (TIMER) database, 2 hub genes showed negative correlations with tumor purity and positive correlations with infiltrating levels of immune filtrating cells. What’s more, we propose new treatment strategies for the two prognostic subtypes. Low- risk patients were found presenting with a higher level of immune checkpoint molecules and showing higher immunogenicity in immunophenoscore (IPS) analysis, which indicated a better response for immunotherapy. Meanwhile, estimated by Genomics of Drug Sensitivity in Cancer (GDSC) database, the high-risk patients showed sensitive responses to five chemotherapy drugs. Finally, 10 candidate small-molecule drugs for CESC were defined. In summary, the CD1C-CD6 signature can accurately predict the prognosis of CESC.  相似文献   
5.
一例吉尔伯特综合征患儿自幼反复出现巩膜黄染,无其他自觉症状;血清胆红素水平升高,以非结合胆红素为主;排除胆道梗阻、溶血等其他引起黄疸的因素;基因检测发现患儿尿苷二磷酸葡糖苷酸转移酶1A1(UGT1A1)基因存在UGT1A1*28和c.211G>A杂合突变。  相似文献   
6.
7.
8.
目的:探讨桃红四物汤治疗腰椎间盘突出症的作用机制。方法:借助中药整合药理学平台,结合中医药大数据,按照“中药-成分-靶标-通路”关联性研究,探讨其治疗腰椎间盘突出的作用机制。结果:共得到桃红四物汤有效成分69个和腰椎间盘突出症的相关靶点396个,进行映射得到48个共同靶点。进行蛋白质-蛋白质相互作用(PPI)网络及其拓扑分析后得到含有203个节点的PPI网络,可能是桃红四物汤治疗LDH的重要靶点。进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析得到各排名前20的生物过程、分子功能、细胞组分和KEGG信号通路,生物过程涉及对脂多糖的反应、对细菌起源分子的反应等;分子功能涉及丝氨酸水解酶活性、细胞因子受体结合等;细胞组分涉及膜筏、膜微区等;KEGG信号通路涉及AGE-RAGE、TNF、IL-17等。结论:桃红四物汤通过多种通路对腰椎间盘突出症产生治疗作用,生物学机制可能与AGE-RAGE、TNF、IL-17等有关。  相似文献   
9.
ObjectivesSjögren's syndrome (SS) is a chronic autoimmune disease characterized by inflammatory lesions in the salivary and lacrimal glands, which are caused by distinct lymphocytic infiltrates. Female non-obese diabetic (NOD) mice spontaneously develop inflammatory lesions of the salivary glands with SS-like pathological features. Previous studies have shown that MyD88, a crucial adaptor protein that activates innate immune signaling, affects lymphocytic infiltration, but its detailed role remains unclear. In this study, we investigated the role of MyD88 through gene expression profiling in the early phase of pathogenesis in the salivary glands of female NOD mice.MethodsSubmandibular glands collected from 10-week-old female wild-type and Myd88-deficient NOD mice were used for RNA preparation, followed by microarray analysis. The microarray dataset was analyzed to identify Myd88-dependent differentially expressed genes (DEGs). Data generated were used for GO enrichment, KEGG pathway, STRING database, and INTERFEROME database analyses.ResultsMyd88 deficiency was found to affect 230 DEGs, including SS-associated genes, such as Cxcl9 and Bpifa2. Most of the DEGs were identified as being involved in immunological processes. KEGG pathway analysis indicated that the DEGs were putatively involved in autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. Furthermore, the DEGs included 149 interferon (IFN)-regulated genes.ConclusionsMyD88 is involved in the expression of specific genes associated with IFN-associated immunopathological processes in the salivary glands of NOD mice. Our findings are important for understanding the role of MyD88-dependent innate immune signaling in SS manifestation.  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