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The IL-7 receptor specific α chain, CD127, can be expressed both as a membrane-associated (mCD127) and a soluble form (sCD127), however, the mechanisms involved in their regulation remain to be defined. We first demonstrated in primary human CD8+ T cells that IL-7-induced downregulation of mCD127 expression is dependent on JAK and PI3K signaling, whereas IL-7-induced sCD127 release is also mediated by STAT5. Following stimulation with IL-7, expression of alternatively spliced variants of the CD127 gene, sCD127 mRNA, is reduced, but to a lesser degree than the full-length gene. Evaluation of the role of proteases revealed that MMP-9 was involved in sCD127 release, without affecting the expression of mCD127, suggesting it does not induce direct shedding from the cell surface. Since defects in the IL-7/CD127 pathway occur in various diseases, including HIV, we evaluated CD8+ T cells derived from HAART-treated HIV-infected individuals and found that IL-7-induced (1) downregulation of mCD127, (2) release of sCD127, and (3) expression of the sCD127 mRNA were all impaired. Expression of mCD127 and sCD127 is, therefore, regulated by distinct, but overlapping, mechanisms and their impairment in HIV infection contributes to our understanding of the CD8+ T cell dysfunction that persists despite effective antiretroviral therapy.  相似文献   
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ABSTRACT

Introduction: Recent data on the 2-drug regimen (2DR) with dolutegravir (DTG) plus lamivudine (3TC) have shown high efficacy and tolerability both in treatment-naïve and experienced HIV-positive patients. Current guidelines recommend DTG+3TC as an alternative to triple antiretroviral therapy (ART) in selected patients to reduce long-term toxicity and costs.

Areas covered: This review is intended to provide insight about the efficacy, safety, and tolerability of a 2DR with DTG+3TC in naïve and treatment-experienced patients.

Expert opinion: Data from clinical trials and from real-life show that DTG+3TC is an effective and safe switch option for the treatment of experienced patients. In treatment-naïve patients, DTG+3TC has shown non-inferiority compared to standard 3-drug regimens but is less effective in severely immunocompromised naïve patients (i.e. with a CD4+ cell count below 200 cell/mm3); furthermore, current guidelines have upgraded this dual regimen to recommended first-line strategy, but indicate that it should not be used without genotypic resistance results. Moreover, this regimen is not feasible for HBV-coinfected individuals and should not be used during pregnancy. Currently, out of 2-drug regimens, DTG+3TC is one of clinicians’ preferred option as it requires no pharmacokinetic booster, has a low risk of drug interaction, and does not require food intake.  相似文献   
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目的:通过调查接受HAART治疗的HIV/AIDS患者的症状分布规律,探讨该类患者的中医证候特点。方法:选取接受HAART治疗3个月以上的HIV/AIDS患者1718例进行横断面调查,采集中医四诊信息和现代生物学信息,对这些患者进行症状、体征、证候出现频率(次)的描述性统计。结果:常见症状依次为:乏力、纳呆、咳嗽、头痛、月经失常(女性)、关节痛、皮肤瘙痒、腰痛、肌肉痛、发热;舌色以红、绛红、淡白及紫色为主,舌形以薄舌、胖大舌、齿痕舌为主,舌苔则以薄白苔和黄腻、厚腻苔多见;脉象以复合脉象为主,分解后脉象以细脉、滑脉、弦脉最为多见。共出现中医证型24种,气血两亏、气阴两虚是最常见的证型,其次为痰热内扰证、肝郁气滞火旺证、脾肾亏虚及湿邪阻滞证。多为复合证型,分解后出现的单证达32种。单证以虚证为主,其次为实证,虚实夹杂最少。脏腑的发病率由高至低依次为脾、肺、肾、肝、心,其中脾系发病率最高,且常与肺、肝、肾合而为病。发病脏腑数目由高至低依次为:三脏同病、二脏同病、四脏同病、一脏发病、五脏同病。结论:接受HAART治疗的HIV/AIDS患者临床症状体征表现多样,病情复杂,证候多见虚实夹杂,以虚为主,涉及脏腑主要为脾、肺、肾,常见多脏腑同病。  相似文献   
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BackgroundCardiovascular dysfunction is a recognized complication of HIV infection in children. Cardiac complications of HIV usually occur late in the course of the disease; they may be associated with drug therapy, and hence become more common as therapy and survival improve. Left ventricular (LV) dysfunction at baseline is a risk factor for death independent of the CD4 cell count, HIV viral load, and neurological disease.ConclusionImmunological recovery following a switch of a failing or potentially cardiotoxic HAART in addition to improved HAART adherence may result in resolution of left ventricular dysfunction. Early and regular cardiology evaluation may improve outcomes in these patients.  相似文献   
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目的 探讨艾滋病抗病毒治疗患者失访发生的相关影响因素,为HIV/AIDS患者管理提供依据。方法 收集2005年6月-2018年12月在南宁市第四人民医院进行抗病毒治疗的艾滋病抗病毒治疗患者为研究对象,使用Excel的RAND随机函数生成的随机数字由小到大进行排序,选取排序前200例的HAART失访的患者为观察组,对照组为在治疗的艾滋病患者中随机选取的200例。采用Logistic回归分析方法分析患者性别、年龄、基线CD4+T淋巴细胞计数、传播途径、基线疾病分期、目前疾病分期、最近1次CD4+T淋巴细胞计数、领药、婚姻状况、子女人数、地区、药物不良反应等12项因素与失访的关系。结果 观察组接受HAART 12个月内失访85例,占总失访人数的42.5%,24个月内失访123例,占总失访人数的61.5%。将12个因素进行多因素logistic回归分析,最终进入回归模型的因素为传播途径、最近1次CD4+T淋巴细胞、药物不良反应,其调整的OR值及OR95%CI分别为6.26(2.99~13.10)、8.68(4.32~17.45)、10.52(2.77~40.00)。结论 HIV/AIDS患者HAART 失访大部分发生在开始治疗的2年内,对出现HAART有不良反应的患者进行及时处理或更换治疗方案,强化对注射吸毒、治疗后CD4+T淋巴细胞提升不理想HIV/AIDS感染者的个体指导和警示教育,增强患者治疗信心,减少失访的发生。  相似文献   
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There remains great controversy as to whether mouse mammary tumor virus (MMTV), the etiological agent of mammary cancer in mice, or a closely related human retrovirus, plays a role in the development of breast cancer in humans. On one hand, retroviruses such as human T‐cell lymphotropic virus and human immunodeficiency virus (HIV) are known causative agents of cancer (in the case of HIV, albeit, indirectly), but attempts to associate other retroviruses with human cancers have been difficult. A recent, high profile, example has been the postulated involvement of another mouse virus, xenotropic murine leukemia virus‐related virus, in human prostate cancer, which is now thought to be due to contamination. Here, we review some of the more recent evidence for and against the involvement of MMTV in human breast cancer and suggest future studies that may allow a definitive answer to this conundrum.  相似文献   
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