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   13020篇
  免费   830篇
  国内免费   375篇
耳鼻咽喉   27篇
儿科学   298篇
妇产科学   245篇
基础医学   2186篇
口腔科学   128篇
临床医学   1073篇
内科学   2560篇
皮肤病学   85篇
神经病学   592篇
特种医学   335篇
外科学   1264篇
综合类   1744篇
预防医学   703篇
眼科学   72篇
药学   2112篇
  4篇
中国医学   444篇
肿瘤学   353篇
  2023年   74篇
  2022年   100篇
  2021年   264篇
  2020年   240篇
  2019年   260篇
  2018年   259篇
  2017年   305篇
  2016年   315篇
  2015年   359篇
  2014年   597篇
  2013年   879篇
  2012年   689篇
  2011年   807篇
  2010年   723篇
  2009年   655篇
  2008年   704篇
  2007年   706篇
  2006年   696篇
  2005年   632篇
  2004年   593篇
  2003年   488篇
  2002年   388篇
  2001年   373篇
  2000年   299篇
  1999年   267篇
  1998年   196篇
  1997年   195篇
  1996年   201篇
  1995年   202篇
  1994年   153篇
  1993年   132篇
  1992年   100篇
  1991年   115篇
  1990年   108篇
  1989年   81篇
  1988年   77篇
  1987年   90篇
  1986年   78篇
  1985年   105篇
  1984年   97篇
  1983年   66篇
  1982年   74篇
  1981年   77篇
  1980年   66篇
  1979年   62篇
  1978年   39篇
  1977年   42篇
  1976年   29篇
  1975年   28篇
  1973年   33篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
目的 探讨糖化血红蛋白(Glycosylated hemoglobin,HbA1c)、空腹胰岛素(Fasting insulin,INS)及服糖后2小时胰岛素(Insulin 2 hours after oral glucose tolerance test,INS-2H)与高血压发病的风险。方法 本研究采用全人群多阶段整群随机抽样方法,抽取了贵州省12个区(县)的48个乡镇共9 280人进行调查,排除基线HbA1c、INS及INS-2H缺失及有高血压病史者,最终纳入1 684例进入分析。中位随访6.23年。采用Cox生存回归分析HbA1c、INS及INS-2H与高血压发病的相关性。PAF及Survival计算人群归因危险百分比。结果 HbA1c和INS-2H每升高一个单位,高血压发病风险分别增加31.5%和1.1%。HbA1c高水平组发病风险是低水平组的2.87倍。相比第一分位组,INS-2H第四分位组发病风险增加73.6%。HbA1c水平控制在6.3 mmol/L及以下可降低人群8.6%的发病。INS-2H水平分别控制在8.81 mIU/L、15.60 mIU/L、24.30 mIU/L以下,可降低人群22.6%、11.9%和6.8%的发病。年龄>42岁组的人群中,HbA1c高水平组发病风险是低水平组的2.84倍; INS-2H第二、三、四分位组发病风险分别是第一分位组的2.001倍、2.145倍和2.145倍。男性人群中,HbA1c高水平组发病风险是低水平组的2.760倍; INS-2H第三、四分位组发病风险是第一分位组的1.828倍和2.116倍。结论 HbA1c及INS-2H是高血压发病的危险因素,在年龄>42岁和男性人群更为敏感。控制HbA1c及INS-2H能有效降低人群高血压发病。  相似文献   
2.
目的探讨妊娠期糖尿病(GDM)患者产后糖代谢异常(AGM)转归及其影响因素。方法选择2019年1月至12月,于四川大学华西第二医院孕期被诊断为GDM,并于产后4~12周进行75 g口服葡萄糖耐量试验(OGTT)筛查的1175例单胎妊娠产妇为研究对象。根据其产后糖代谢是否正常,将其分为研究组(n=361,产后AGM者)与对照组(n=814,产后糖代谢正常者)。采用回顾性分析方法,收集受试者一般临床资料及孕期与产后4~12周75 g OGTT结果等,并采用成组t检验或χ^(2)检验进行统计学分析。对GDM患者产后AGM转归相关影响因素进行单因素分析与多因素非条件logistic回归分析,探讨其AGM转归的独立影响因素。本研究遵循的程序符合病例收集医院伦理委员会制定的伦理学标准,得到该伦理委员会批准[审批文号:医学科研2021伦审批第(181)号]。结果①24~28孕周时,1175例GDM患者75 g OGTT结果提示,空腹血糖(FPG)及OGTT 1、2 h血糖指标中,1、2、3项升高者分别为639例(54.4%)、373例(31.7%)与163例(13.9%)。②产后4~12周时,1175例GDM患者75 g OGTT结果提示,产后糖代谢正常者为814例(69.3%),AGM为361例(30.7%),包括空腹血糖受损(IFG)为19例(1.6%),糖耐量受损(IGT)为294例(25.0%),IFG+IGT为23例(2.0%),疑似2型糖尿病(T2DM)患者为25例(2.1%)。③产后AGM转归影响因素的单因素分析结果显示,研究组GDM患者年龄、糖尿病家族史发生率,24~28孕周OGTT 1、2 h血糖值,以及2项血糖指标(OGTT 1、2 h血糖)均升高与3项血糖指标(FPG及OGTT1、2 h血糖)均升高者所占比例,均显著高于对照组,而研究组仅1项血糖指标(FPG或OGTT 1 h血糖)升高者所占比例,则显著低于对照组,2组比较,差异均有统计学意义(P<0.05)。④多因素非条件logistic回归分析结果:模型1将受试者年龄、糖尿病家族史及24~28孕周OGTT 1、2 h血糖值进行多因素logistic回归分析结果显示,糖尿病家族史及24~28孕周OGTT 1、2 h血糖值,均为GDM患者产后AGM转归的独立危险因素(OR=1.693、1.205、1.355,95%CI:1.208~2.373、1.088~1.335、1.204~1.524,P=0.002、<0.001、<0.001)。模型2将受试者年龄、糖尿病家族史、24~28孕周OGTT血糖指标升高项目进行多因素logistic回归分析结果显示,糖尿病家族史及24~28孕周OGTT 2项血糖指标(OGTT 1、2 h血糖)升高与3项血糖指标均升高,均为GDM患者产后AGM转归独立危险因素(OR=1.668、1.421、1.747,95%CI:1.192~2.333、1.035~1.952、1.195~2.553,P=0.003、0.030、0.004);24~28孕周仅FPG或OGTT 1 h血糖升高为其独立保护因素(OR=0.401、0.646,95%CI:0.240~0.670、0.418~0.997,P<0.001、=0.048)。结论对于GDM患者产后AGM转归,临床应关注其年龄、糖尿病家族史、孕期OGTT结果等指标。对GDM高危人群进行上述指标持续监测与规范干预,是健全GDM孕前-孕期-产后全程管理的重要环节。  相似文献   
3.
目的探讨雌二醇对小鼠颈部移植心脏免疫耐受的影响。方法建立小鼠颈部心脏异位移植模型,供、受体均为近交系健康雄性BALB/c和C57BL/6小鼠,分别在受体小鼠心脏移植术后1 d,3 d,7 d腹腔注射不同剂量外源性雌二醇实现干预。实验分为4组:A组:对照组,供、受体均无特殊处理;B组:2 mg/kg;C组:4 mg/kg;D组:6 mg/kg。术后观察比较各组受体小鼠供心存活时间、排斥反应程度及冠状动脉内膜增生程度。结果B、C、D组受体小鼠比A组存活天数明显延长[(13.7±1.6)d、(15.3±1.9)d、(16.7±2.2)d与(8.8±1.3)d,P<0.05],B、C、D组之间相比,随着外源性雌二醇注射剂量的增加存活天数有所延长,但差异无统计学意义。切取移植后供心进行苏木精-伊红染色病理检查发现:术后第7天B、C、D组心肌组织间存在多灶型炎症细胞浸润并伴有部分心肌坏死,但是移植心发生排斥反应的程度轻于A组,术后第7天排斥分级显示D组移植小鼠明显较A组小鼠排斥反应轻。通过弹力纤维染色图像分析测定发现各组移植心脏冠状动脉内膜增厚程度随着存活天数的延长而加重,术后7 d给予B、C、D组冠状动脉内膜增生慢,且随着外源性雌二醇注射剂量的增加,冠状动脉内膜增生更慢。结论雌二醇干预能够抑制免疫排斥反应,减轻冠状动脉内膜增生,延长移植心脏存活时间,在诱导小鼠移植心脏产生免疫耐受方面具有一定作用。  相似文献   
4.
In liver transplant patients, solid tumors and post-transplant lymphoproliferative disorders have emerged as significant long-term mortality causes. In addition, it is assumed that de novo malignancy after liver transplantation (LT) is the second-leading cause of death after cardiovascular complications. Well-established risk factors for post-transplant lymphoproliferative disorders and solid tumors are calcineurin inhibitors, tacrolimus, and cyclosporine, the cornerstones of all immunosuppressive therapies used after LT. The loss of immunocompetence facilitated by the host immune system due to prolonged immunosuppressive therapy leads to cancer development, including LT patients. Furthermore, various mechanisms such as bacterial dysbiosis, activation through microbe-associated molecular patterns, leaky gut, and bacterial metabolites can drive cancer-promoting liver inflammation, fibrosis, and genotoxicity. Therefore, changes in human microbiota composition may contribute further to de novo carcinogenesis associated with the severe immunosuppression after LT.  相似文献   
5.
Background and aimsDeterioration of anthropometric and lung function parameters was shown to precede the onset of cystic fibrosis-related diabetes (CFRD) in adults. In children, studies have been conducted in small cohorts with relatively short observation period. Study objectives were to document the longitudinal trends of anthropometric, pulmonary, nutritional and metabolic parameters from cystic fibrosis (CF) diagnosis to the ascertainment of abnormal glucose tolerance and identify parameters associated with the incidence of such abnormalities in a pediatric CF cohort.Methods and resultsRetrospective cohort study of 281 children with CF. Longitudinal trends of anthropometric, lung function, nutritional and metabolic data were generated from CF diagnosis to the ascertainment of abnormal glucose tolerance defined as the presence of either impaired glucose tolerance (IGT), unconfirmed CFRD or CFRD. Cox models and Kaplan–Meier curves were used to identify factors associated with developing abnormal glucose tolerance.Forty-five percent of cohort had normal glucose tolerance (NGT), 27% IGT, 10% unconfirmed CFRD and 18% CFRD. Children who developed CFRD displayed lower height z-scores from a very early age. Conversely, HbA1c levels began to rise closer to CFRD ascertainment. Height z-scores (HR: 0.45; CI 95% [0.29–0.69]) and HbA1c (HR: 2.43; CI 95% [1.86–3.18]) in years preceding ascertainment were associated with the risk of developing CFRD.ConclusionChildren who developed CFRD display distinctive trends for height z-scores from a very early age, whereas HbA1c appears as a marker of established glucose metabolism derangements.  相似文献   
6.
目的 探讨高血压合并糖耐量减低(IGT)对老年男性人群全因死亡风险的影响。方法 纳入2005年5月至2007年5月在解放军总医院第二医学中心行口服葡萄糖耐量试验检出的老年男性IGT患者和正常糖耐量(NGT)人群,根据基线时是否存在高血压病史和IGT分为4组:非高血压(NH)+正常糖耐量(NGT)组、高血压(H)+NGT组、NH+IGT组、H+IGT组,每年至少随访1次。采用SPSS 13.0统计软件进行数据分析。采用Cox回归模型分析不同组别全因死亡风险的差异。结果 与NH+NGT组比较,H+IGT组(HR=2.55,95%CI 1.56-4.16; P<0.001)和NH+IGT组(HR=2.40,95%CI 1.35-4.25; P=0.003)2型糖尿病发病风险显著升高。单因素Cox比例风险回归分析提示,与NH+NGT组比较,H+IGT组(HR=2.59,95%CI 1.34-5.01; P=0.005)全因死亡风险明显升高,而H+NGT组和NH+IGT组无统计学差异(P>0.05)。在调整相关危险因素后多因素Cox比例风险回归分析显示,H+IGT组(HR=1.83,95%CI 0.90-3.70; P=0.095)全因死亡风险较NH+NGT组虽无统计学差异(P>0.05),但有升高的趋势。结论 老年男性人群高血压合并IGT与全因死亡风险密切相关,高血压与IGT并存可导致全因死亡风险增加。  相似文献   
7.
《Pancreatology》2021,21(6):1112-1118
ObjectiveTo determine the risk association between fasting glucose levels and pancreatic cancer using systematically collected prediagnostic blood glucose samples.MethodsProspective nested case-control study of participants from the Northern Sweden Health and Disease Study, including 182 cases that developed pancreatic cancer and four matched controls per case. Blood glucose levels collected up to 24 years before pancreatic cancer diagnosis were analyzed. The association between fasting glucose levels and pancreatic cancer risk was determined using unconditional and conditional logistic regression models. The association between fasting glucose and the time to pancreatic cancer diagnosis, tumor stage and survival was determined using likelihood-ratio test, t-test and log rank test.ResultsThe unadjusted risk of developing pancreatic cancer increased with increasing fasting glucose levels (OR 1.30, 95% CI 1.05–1.60, P = .015). Impaired fasting glucose (≥6.1 mmol/L) was associated with an adjusted risk of 1.77 for developing pancreatic cancer (95% CI 1.05–2.99, P = .032). In subgroup analysis, fasting glucose levels were associated with an increased risk in never-smokers (OR 4.02, 95% CI 1.26–12.77, P = .018) and non-diabetics (OR 3.08, 95% CI 1.08–8.79, P = .035) (non-significant for interaction). The ratio between fasting glucose and BMI was higher among future pancreatic cancer patients and an increased ratio was associated with elevated risk of pancreatic cancer (OR 1.66, 95% CI 1.04–2.66, P = .034). Fasting glucose levels were not associated with TNM stage at diagnosis or survival.ConclusionsHigh fasting glucose is associated with an increased risk of being diagnosed with pancreatic cancer.  相似文献   
8.
Central B cell tolerance, the process restricting the development of many newly generated autoreactive B cells, has been intensely investigated in mouse cells while studies in humans have been hampered by the inability to phenotypically distinguish autoreactive and nonautoreactive immature B cell clones and the difficulty in accessing fresh human bone marrow samples. Using a human immune system mouse model in which all human Igκ+ B cells undergo central tolerance, we discovered that human autoreactive immature B cells exhibit a distinctive phenotype that includes lower activation of ERK and differential expression of CD69, CD81, CXCR4, and other glycoproteins. Human B cells exhibiting these characteristics were observed in fresh human bone marrow tissue biopsy specimens, although differences in marker expression were smaller than in the humanized mouse model. Furthermore, the expression of these markers was slightly altered in autoreactive B cells of humanized mice engrafted with some human immune systems genetically predisposed to autoimmunity. Finally, by treating mice and human immune system mice with a pharmacologic antagonist, we show that signaling by CXCR4 is necessary to prevent both human and mouse autoreactive B cell clones from egressing the bone marrow, indicating that CXCR4 functionally contributes to central B cell tolerance.

The bone marrow tissue is the major site of postnatal B cell development in both mice and humans (1, 2). B lymphopoiesis begins when hematopoietic stem cells (HSCs) differentiate into common lymphoid progenitors that commit to the B cell lineage by developing into precursors of B cell progenitors (3). These precursors undergo a step-by-step differentiation process that is accompanied by the rearrangement of V, D, and J gene segments at the immunoglobulin (Ig) heavy chain locus first and then, after a heavy (H) chain is expressed, of V and J segments at the Ig light chain loci, Igκ and Igλ (4). The de novo synthesized H and L Ig chains pair with the signaling molecules CD79A and CD79B to form a B cell receptor (BCR) that is expressed on the cell surface as IgM and that functions as antigen receptor (5). These newly generated IgM+ B cells, which are identified as immature B cells, undergo further differentiation into transitional B cells that enter the circulation and complete their maturation in the spleen (6).A feature of B cell development is that the assembly of the Ig H and L chain genes occurs through random reassortment of numerous V(D)J gene segments, which facilitates the generation of a vast number of antibody specificities, one per each developing B cell (4). While this feature is crucial to the development and maintenance of a B cell population and antibody repertoire capable of recognizing any pathogen, the disadvantage is that the majority of these V(D)J gene sequences encode antibodies that are self-reactive (7, 8). It is well established that the entry of newly generated autoreactive B cell clones into the peripheral tissue is restricted by the physiological process of tolerance, a process that evolved to reduce the chance of autoantibody responses and autoimmunity. Indeed, antibody repertoire studies in mice and humans as well as studies with Ig transgenic and knock-in mice have amply demonstrated that the transition from the bone marrow immature B cell stage to the peripheral B cell stage is accompanied by a significant decrease (about twofold) in the frequency of autoreactive clones (8, 9), and this is because clones with BCRs that exhibit high avidity for self-antigens are prevented from entering the peripheral B cell population (1012).The process of central B cell tolerance has been mainly characterized in mouse models where it operates via the maintenance of RAG1/2-mediated VJ recombination at the light chain loci (i.e., receptor editing) and by inducing cell death (i.e., clonal deletion) in clones in which receptor editing fails to provide a nonautoreactive specificity within a few days (1316). A major bottleneck in studying central B cell tolerance in humans is the difficulty of acquiring fresh bone marrow samples and the inability to identify and distinguish autoreactive from nonautoreactive B cell clones. Single-cell cloning of Ig genes from newly formed bone marrow B cells that emigrated into the blood, together with the expression and testing of the antibodies they encode, have provided estimates of the efficiency of central B cell tolerance in humans (7, 17). These studies have elegantly shown that central B cell tolerance is significantly less efficient in many autoimmune patients, and particularly in those with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type-1 diabetes (T1D), and Sjögren’s syndrome (1822). These studies have further shown that the genetic variant R620W of the PTPN22 protein tyrosine phosphatase, a variant linked to a higher risk for the development of autoimmunity, is also associated with higher frequencies of autoreactive/polyreactive clones among the new emigrant transitional B cells, revealing a defective central tolerance checkpoint in individuals carrying this risk allele (23).To elucidate mechanisms of development and tolerance of human B cells, our group has investigated human immune system humanized mice (HIS hu-mice) in which human B lymphocytes develop subsequent to the engraftment of human umbilical cord blood HSCs (24, 25). With this intent, we have previously created a HIS hu-mouse model in which all mouse cells express a synthetic membrane-bound self-antigen (Hcκ) that reacts at high avidity with developing human Igκ+ B cells (26). In this model, all human κ+ B cells are autoreactive and undergo central tolerance in the bone marrow via a mix of receptor editing and clonal deletion (26).In the present study we aimed to exploit this HIS hu-mouse model to discover markers that distinguish human autoreactive immature B cells from nonautoreactive cells, as well as to identify pathways that contribute mechanistically to the enforcement of central B cell tolerance. Our data show that human autoreactive immature B cells contrast from nonautoreactive cells by up-regulating CD69 and CXCR4 while downmodulating the expression of IgM, CD19, CD81, and BAFFR as well as maintaining lower ERK activation. Cells with a similar phenotype, although more subtle, were also observed within the developing immature B cell population of human bone marrow specimens. Moreover, small differences in the expression of these markers and in the amount of sera autoantibodies were found in HIS hu-mice generated with HSCs from some donors genetically predisposed to autoimmunity. Finally, our data demonstrate that retention of human autoreactive B cells in the bone marrow does not rely on CD69 expression while is critically dependent on CXCR4 signaling, indicating that the CXCR4–CXCL12 pathway enforces central B cell tolerance.  相似文献   
9.
目的:探讨超纯水透析液对维持性血液透析病人贫血、血浆内毒素及炎症因子水平的影响。方法:选取2018年3月—2019年3月维持性血液透析病人86例为研究对象,根据随机数字表法将病人分为观察组与对照组各43例。对照组行常规血液透析治疗,观察组应用超纯水透析液行维持性血液透析治疗,治疗时间均为6个月,比较两组病人贫血情况、血浆内毒素及炎症因子水平。结果:干预后观察组病人血红蛋白(Hb)及红细胞比容(HCT)水平明显高于对照组(P<0.05),每周重组人促红细胞生成素用量少于对照组(P<0.05),血浆内毒素、C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)含量低于对照组(P<0.05)。结论:应用超纯水透析液行血液透析治疗能有效降低病人血浆内毒素及炎症因子水平,能明显纠正透析病人贫血,提高病人血液透析效果。  相似文献   
10.
目的探讨血府逐瘀汤加减对血瘀阻滞型稳定型冠心病心绞痛的临床意义以及药理研究。方法选取2019年1月—2020年5月在沈阳市苏家屯区中西医结合医院的80例血瘀阻滞型稳定型冠心病心绞痛患者,随机分组。对照组40例患者给予常规西医药进行治疗;试验组40例在对照组的基础上采取血府逐瘀汤加减治疗,比较2组患者治疗后运动耐量情况,即:患者运动后心绞痛人数,ST压低≥1 mm人数以及心率达亚极量人数。结果试验组患者接受治疗后到达运动心绞痛人数,终点情况ST压低≥1 mm人数以及心率达亚极量人数均低于对照组患者,差异有统计学意义(P<0.05)。结论对血瘀阻滞型稳定型冠心病心绞痛患者来说,血府逐瘀汤加减对其临床疗效显著,故该药方应作为辅助治疗方案。  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