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目的基于UHPLC-Q-Exactive-Orbitrap-MS技术阐明树舌灵芝主要成分,结合网络药理学探讨其防治新型冠状病毒肺炎的作用机制。方法采用UHPLC-Q-Exactive-Orbitrap-MS技术鉴定树舌灵芝的主要成分;采用Swiss Target Prediction数据平台对鉴定成分进行靶点预测,对核心靶基因进行GO和KEGG富集分析,运用Cytoscape 3.8.0绘制关联网络图,同时通过分子对接评价树舌灵芝核心成分与血管紧张素转化酶Ⅱ(ACE2)及3种新型冠状病毒(SARS-CoV-2)蛋白的结合作用。结果该研究从树舌灵芝中鉴定化合物62个;30个活性化合物主要作用在IL-6、PTGS2和MAPK1等32个核心靶点,通过PI3K/Akt、TNF及肺结核等多条与肺损伤保护相关通路,发挥防治COVID-19的作用;分子对接显示小白菊内酯、1,4-二羟基-2-萘甲酸和瑞香素等核心成分与ACE2及3种SARS-CoV-2蛋白的亲和作用较好。结论该研究初步阐明树舌灵芝的化学成分及潜在作用机制,为筛选树舌灵芝防治COVID-19的药效成分及深入阐明作用机制提供了科学的理论依据。 相似文献
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目的:探讨表皮生长因子蛛毒素受体7 穿膜结构域蛋白1(ELTD1)在肾透明细胞癌(ccRCC)组织中的表达、甲基化水 平及其与患者临床病理特征和预后的相关性。方法:通过公共数据库分析ccRCC 组织中ELTD1 表达和甲基化的差异水平,探讨 ELTD1 表达水平与患者临床病理特征和预后的相关性。通过TIMER2.0 数据库评估ccRCC 免疫细胞浸润,筛选ELTD1 相关免疫 检查点基因,进行GO 功能和KEGG 通路富集分析,通过基因共表达分析、筛选与ELTD1 相关的基因。结果:与癌旁组织比较,ELTD1 在ccRCC 组织中呈高表达(P<0.05)。TCGA-KIRC 队列中,ELTD1 的甲基化水平与其表达呈负相关(R=-0.37,P<0.01)。 ELTD1 转录表达在ccRCC 患者年龄、T 分期、M 分期、临床分期及病理分级组间存在显著差异(均P<0.01),且高表达ELTD1 与较 长的OS 和PFS 密切相关(HR=0.55、0.63,均P<0.01),ELTD1 高表达是ccRCC 的独立保护因素。ELTD1 表达与B 细胞、CD4+ T 细 胞、CD8+ T 细胞、巨噬细胞和嗜中性粒细胞的免疫浸润呈显著负相关(R=-0.16、-0.27、-0.25、-0.31、-0.27,均P<0.01)。GO 功能和 KEGG 通路富集分析结果显示,血管生成及肿瘤相关信号通路在ELTD1 高表达表型中显著富集(均P<0.01)。ELTD1 共表达基因 的生存分析提示,其肿瘤抑制作用与共表达网络有关。结论:ELTD1 在ccRCC 组织中高表达和低甲基化是患者预后良好的指标,且与免疫浸润相关。 相似文献
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《Diagnostic Histopathology》2022,28(9):424-430
Metastatic brain disease frequently complicates extra central nervous system (CNS) neoplastic disease, with an increase in reported incidence over time. Brain parenchyma is the commonest anatomical site, with other lesions involving the spinal cord, dura and tissues surrounding the CNS. Metastases are usually characterised by a well-defined border with surrounding brain, although some can show an infiltrative edge. The use of appropriate immunohistochemical panels can help identify the origin of most tumours, and molecular testing should be performed according to the site of origin even if performed on a previous specimen due to potential changes in molecular characteristics. Reliable detection of leptomeningeal metastasis using CSF cytology relies on examination of an adequate volume of fluid; immunocytochemistry and flow cytometry can also be useful in the correct settings. Advances in the field include liquid biopsies, where circulating biomarkers are examined, and the use of methylation profiling to identify primary tumours. 相似文献
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目的 基于网络药理学方法和分子对接技术探究冬虫夏草抗肿瘤的作用机制。方法 利用TCMSP、CNKI、PubMed、Drugbank、Stitch和Swiss target prediction等平台检索冬虫夏草的化学成分和作用靶点;通过GeneCards、OMIM等数据库筛选肿瘤相关基因,运用Cytoscape 3.7.2构建冬虫夏草活性成分-靶点网络,通过String数据库对关键靶点构建网络互作(PPI)网络,并进行基因本体(GO)基因和京都基因和基因组百科全书(KEGG)通路富集分析,最后利用AutoDock Vina软件和Pymol软件对药物有效活性成分和关键靶点进行分子对接验证。结果 共得到冬虫夏草22个化合物,86个抗肿瘤共同靶点,主要包括环加氧酶(PTGS)2、丝裂原活化蛋白激酶3(MAPK3)、过氧化物酶体增生激活受体γ(PPARG)、胱天蛋白酶3(CASP3)、JUN基因等关键靶点。GO分析与KEGG通路结果显示,冬虫夏草抗肿瘤涉及到多种生物学过程以及PPAR、花生四烯代谢、5-羟色胺信号通路等多种信号通路。将关键化合物和靶点进行分子对接,提示冬虫夏草抗肿瘤可能的前5个主要活性成分11,14-二十碳二烯酸、花生四烯酸、黄豆黄素、胆甾醇和豆甾醇与关键靶点PTGS2、PTGS1、PGR、HMGCR和CNR1均能自发结合。结论 初步探讨了冬虫夏草抗肿瘤的主要活性成分、相关靶点及相关通路,发现冬虫夏草可以通过多成分、多靶点、多通路抗肿瘤,为后期实验验证提供了参考依据。 相似文献
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Evaluation of KISS1 Receptor Gene Expression in Egyptian Female Patients with Breast Cancer 下载免费PDF全文
Salwa Hamdi GomaaMoyassar Ahmed ZakiMohamed Hussein SultanFatma Ibrahim DwedarEman Hassan Elzain Zidan 《Asian Pacific journal of cancer prevention》2022,23(3):961-969
Objective: Breast cancer is the second most common cancer in the world. Many metastasis suppressor genes were identified, including the KISS1 gene which encodes for a 145 amino acid protein (kisspeptin-145), which undergoes proteolytic cleavage resulting in kisspeptin-14, -13 and -10. All of these proteins can activate KISS1 receptor (KISS1R). The role of KP/KISS1R signaling in breast cancer remains controversial. The present study aimed to measure mRNA gene expression of KISS1 receptor in healthy and cancerous breast tissue and to evaluate the association of its level with the available molecular subtypes and the traditional clinico-pathological variables. Methods: The study was done on 41 operable primary breast cancer patients. Biopsies from both tumor tissue and surrounding healthy mammary tissue were taken from all patients. KISS1R mRNA expression level was measured using a quantitative real time PCR. Results: KISS1R mRNA expression was significantly higher in stage III patients compared to stage II patients. At a cut-off value for KISS1R mRNA expression of 1.75, stage II was discriminated from stage III. A significant positive correlation was found between KISS1R mRNA expression and tumor size as well as lymph nodes metastasis. KISS1R mRNA was highly expressed in ER negative cases compared to ER positive ones, and in PR negative cases compared to PR positive ones. There was a statistically significant difference in KISS1R mRNA expression levels and different molecular subtypes being over-expressed in HER2 and triple negative cancer cases. Conclusion: This study supports other studies suggesting that KISS1/KISS1R may not be acting as a metastasis suppressor in breast cancer. KISS1R mRNA is over expressed in advanced stages of breast cancer and hence it can be used as a prognostic marker for aggressiveness of breast cancer. Also being over expressed in triple negative patients, KISS1R could represent a promising therapeutic target in triple negative cases. 相似文献
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von Willebrand factor (VWF) plays a crucial role in hemostasis and thrombosis. VWF is involved in platelet attachment to the subendothelium, serving as a carrier protein for coagulation factor VIII. In this study, myocardial tissues from deceased patients with ischemic heart disease and a mouse model of acute myocardial infarction were subjected to immunohistochemistry to determine VWF expression. We examined 28 neutral formalin-fixed, paraffin-embedded myocardial tissue samples obtained from the autopsies of patients who were diagnosed with ischemic heart disease within 48 h postmortem. Most myocardial cells were negative for VWF, although some cells showed nonspecific positivity. Elevated VWF expression was observed around myocardial cells undergoing remodeling, suggesting that endothelial proliferation occurred at these sites. In contrast, completely fibrotic myocardial foci did not show upregulated VWF expression. Positivity in fibrin deposition and hemorrhagic sites was observed. The same VWF expression characteristics as those observed in the human samples were observed in the mouse model. VWF immunostaining as an endothelial marker may be a useful supplementation to conventional staining techniques that are currently used in the diagnosis of ischemic heart disease in terms of examining the timing of myocardial remodeling in detail and highlighting the remodeling process. 相似文献
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《Diagnostic Histopathology》2022,28(5):270-272
We discuss the second reported case of NUT carcinoma (NC) arising in the thyroid.1 NC is a rare and aggressive malignancy which usually arises in the midline head and neck structures. The tumour is defined cytogenetically by rearrangements of the NUTM1 gene, most commonly producing the BRD4-NUTM1 fusion oncogene. A 23-year-old-male had a neck mass excised by right hemithyroidectomy following two fine needle aspirates (Thy 3a and Thy 4). Following completion left thyroidectomy with bilateral central neck dissection, further surgery was required to excise recurrent disease from the thyroid bed and right lateral neck. This aggressive clinical course prompted molecular analysis which revealed a BRD4-NUTM1 fusion gene. The initial hemithyroidectomy diagnosis of solid variant papillary thyroid carcinoma with poorly differentiated areas was thus revised to NC. This is a rare site for NC to occur and illustrates the importance of considering this diagnosis in poorly differentiated neoplasms in the head and neck region.1 相似文献