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1.
《Saudi Pharmaceutical Journal》2022,30(11):1572-1588
Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.  相似文献   
2.
AimTo determine whether convalescent angiotensin (1?7) peptide replacement therapy with plasma (peptide plasma) transfusion can be beneficial in the treatment of critically ill patients with severe coronavirus 2 (SARS-CoV-2) infection.Study designCase series of 9 critically ill patients with laboratory-confirmed COVID-19 who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment.Peptide plasma: Plasma with angiotensin (1?7) content 8–10 times higher than healthy plasma donors was obtained from suitable donors. Peptide plasma transfusion was applied to 9 patients whose clinical status and/or laboratory profile deteriorated and who needed intensive care for 2 days.ResultsIn our COVID-19 cases, favipiravir, low molecular weight heparin treatment, which is included in the treatment protocol of the ministry of health, was started. Nine patients with oxygen saturation of 93% and below despite nasal oxygen support, whose clinical and/or laboratory deteriorated, were identified. The youngest of the cases was 36 years old, and the oldest patient was 85 years old. 6 of the 9 cases had male gender. 3 cases had been smoking for more than 10 years. 4 cases had at least one chronic disease.In all of our cases, SARS CoV2 lung involvement was bilateral and peptide plasma therapy was administered in cases when oxygen saturation was 93% and below despite nasal oxygen support of 5 liters/minute and above, and intensive care was required. Although it was not reflected in the laboratory parameters in the early period, 8 patients whose saturations improved with treatment were discharged without the need for intensive care. However, a similar response was not obtained in one case. Oxygen requirement increased gradually and, he died in intensive care process. An increase of the platelet count was observed in all cases following the peptide plasma treatment.ConclusionIn this preliminary case series of 9 critically ill patients with COVID-19, administration of plasma containing angiotensin (1?7) was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.  相似文献   
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目的 鉴定当地民间应用普遍的野生药用真菌,并探讨其治疗肿瘤的作用机制。方法 采用形态学和分子生物学方法对一株采自定陶仿山野生药用真菌进行鉴定,确定为硬皮马勃。通过文献检索收集硬皮马勃化学成分,利用PubChem软件和TCMSP、GCS数据库得到化学成分结构信息及其药用动力学参数和相关靶点分析,通过SysDT和WES系统鉴定潜在化学成分靶点,利用CTD数据库获得靶点功能,将潜在化合物和肿瘤相关靶点导入Cytoscape3.8.0软件构建分子-靶标网络。应用DAVID数据库对肿瘤相关靶点进行GO和KEGG富集分析,揭示有关活性成分靶点所涉及的生物学过程和通路,将肿瘤相关靶点和通路导入Cytoscape3.8.0软件构建靶点-通路网络。结果 从文献中获得硬皮马勃的化学成分59个,通过ADME计算系统筛选出5个潜在活性的化合物即活性成分,预测到38个靶点,其中与肿瘤相关靶点16个。这些活性成分主要通过Toll-like receptor、PI3K-AKT、MAPK和NF-kappa B等通路参与免疫应答,抑制肿瘤细胞生长、增殖,促进其凋亡。结论 表明硬皮马勃治疗肿瘤具有多靶点、多途径协同作用的特点,并通过多层次效应达到治疗肿瘤的效果。本研究为更好理解硬皮马勃作用肿瘤的机制和肿瘤药物开发提供理论依据。  相似文献   
4.
Mycobacterium tuberculosis (M. tuberculosis) encodes an essential enzyme acetyl ornithine aminotransferase ArgD (Rv1655) of arginine biosynthetic pathway which plays crucial role in M. tuberculosis growth and survival. ArgD catalyzes the reversible conversion of N-acetylornithine and 2 oxoglutarate into glutamate-5-semialdehyde and L-glutamate. It also possesses succinyl diaminopimelate aminotransferase activity and can thus carry out the corresponding step in lysine biosynthesis. These essential roles played by ArgD in amino acid biosynthetic pathways highlight it as an important metabolic chokepoint thus an important drug target. We showed that M. tuberculosis ArgD rescues the growth of ΔargD E. coli grown in minimal media validating its functional importance. Phylogenetic analysis of M. tuberculosis ArgD showed homology with proteins in gram positive bacteria, pathogenic and non-pathogenic mycobacteria suggesting the essentiality of this protein. ArgD is a secretory protein that could be utilized by M. tuberculosis to modulate host innate immunity as its moonlighting function. In-silico analysis predicted it to be a highly antigenic protein. The recombinant ArgD protein when exposed to macrophage cells induced enhanced production of pro-inflammatory cytokines TNF, IL6 and IL12 in a dose dependent manner. ArgD also induced the increased production of innate immune effector molecule NOS2 and NO in macrophages. We also demonstrated ArgD mediated activation of the canonical NFkB pathway. Notably, we also show that ArgD is a specific TLR4 agonist involved in the activation of pro-inflammatory signaling for sustained production of effector cytokines. Intriguingly, ArgD protein treatment activated macrophages to acquire the M1 phenotype through the increased surface expression of MHCII and costimulatory molecules CD80 and CD86. ArgD induced robust B-cell response in immunized mice, validating its antigenicity potential as predicted by the in-silico analysis. These properties of M. tuberculosis ArgD signify its functional plasticity that could be exploited as a possible drug target to combat tuberculosis.  相似文献   
5.
以“七麦数据”网站收录的中医移动医疗App作为研究对象,采用网络调查法和文献分析法,根据“七麦数据”对移动医疗App的分类,结合中医移动医疗App的信息服务内容和特点,将筛选出的中医移动医疗App划分为医疗健康类、中医养生类、知识传播类、全面综合类,并根据“七麦数据”网站中对各类中医移动医疗App的打分及累计下载量筛选出最具代表性的12款中医移动医疗App,从全面性、人性化、安全性、实用性4个一级指标和40个二级指标对其信息服务现状进行评价,指出当前中医移动医疗App信息服务存在的问题并提出建议。  相似文献   
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背景 骨关节炎致残、致畸率高,可合并多种身心疾病,但早期症状不明显。当前社区骨关节炎的管理存在管治不协调、方法不健全、制度不完善等问题。 目的 构建并评价基于信息化的社区骨关节炎多学科管理模式,以促进对社区骨关节炎患者的管理,改善患者疾病预后。 方法 首先构建社区骨关节炎患者的多学科管理模式,包含基于危险因素分层的患者分级管理流程、多学科管理团队及其诊治分工,然后构建基于信息化的多学科管理流程,并完成信息软件开发。选取2019年7月至2020年7月在上海市定海、大桥社区卫生服务中心全科门诊,以及杨浦区中心医院骨科门诊就诊的膝骨关节炎患者80例为研究对象,采用随机数表法将其分为普通组和多学科组,各40例。普通组采用常规治疗模式,多学科组在此基础上进行基于信息化的多学科管理。分别于治疗前和治疗12周后评估两组患者的视觉模拟评分法(VAS)评分、西安大略麦克马斯特大学(WOMAC)骨关节炎指数、关节炎生活质量测量量表(AIMS2)评分、健康素养管理量表(HeLMS)评分、体质指数(BMI)。 结果 治疗前,多学科组和普通组膝骨关节炎患者的VAS评分、WOMAC骨关节炎指数、AIMS2评分、HeLMS评分、BMI比较,差异均无统计学意义(P>0.05);治疗12周后,多学科组和普通组膝骨关节炎患者的VAS评分、WOMAC骨关节炎指数低于治疗前,AIMS2总分、HeLMS总分高于治疗前,差异有统计学意义(P<0.05);治疗12周后,多学科组患者AIMS2总分、HeLMS总分高于普通组,VAS评分、WOMAC骨关节炎指数、BMI均低于普通组,差异有统计学意义(P<0.05)。 结论 对膝骨关节炎患者实施基于信息化的社区骨关节炎患者多学科管理模式,可有效减轻患者的关节疼痛和体质量,提高患者的日常生活能力和健康素养,改善患者的生活质量,延缓患者的病情进展。  相似文献   
9.
BackgroundUnequal housing access resulted in more than 150 million homeless people worldwide, with millions more expected to be added every year due to the ongoing climate-related crises. Homeless population has a counterproductive effect on the social, psychological integration efforts by the community and exposure to other severe health-related issues. Geographic Information Systems (GIS) have long been applied in urban planning and policy, housing and homelessness, and health-related research.MethodsWe used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method to systematically review 24 articles collected from multiple databases (n = 10) that focused on health-related issues among homeless people and used geospatial analysis techniques in their research.ResultsOur findings indicated a geographic clustering of case study locations– 26 out of the 31 case study sites are from the USA and Canada. Studies used spatial analysis techniques to identify hotspots, clusters and patterns of patient location and population distribution. Studies also reported relationships among the location of homeless shelters and substance use, discarded needles, different infectious and non-infectious disease clusters.ConclusionMost studies were restricted in analyzing and visualizing the patterns and disease clusters; however, geospatial analyses techniques are useful and offer diverse techniques for a more sophisticated understanding of the spatial characteristics of the health issues among homeless people. Better integration of GIS in health research among the homeless would help formulate sensible policies to counter health inequities among this vulnerable population group.  相似文献   
10.
吴斌 《中国免疫学杂志》2022,38(2):249-252+258
目前原发性干燥综合征(pSS)诊断仍然依赖于侵入性小涎腺活检手术,常导致其早期诊断异常艰难,因此筛选特定生物标志物可能对pSS诊断和个体化治疗极为有益。本文回顾传统标志物及与B细胞活化和表观遗传相关的新标志物,并综述组学标志物研究进展。尽管生物标志物前景较好,但其可靠性仍需扩大样本量进行验证。  相似文献   
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