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   706篇
  免费   76篇
  国内免费   27篇
耳鼻咽喉   2篇
儿科学   16篇
妇产科学   10篇
基础医学   204篇
口腔科学   11篇
临床医学   43篇
内科学   146篇
皮肤病学   10篇
神经病学   27篇
特种医学   15篇
外国民族医学   1篇
外科学   37篇
综合类   73篇
预防医学   28篇
眼科学   5篇
药学   30篇
中国医学   18篇
肿瘤学   133篇
  2023年   9篇
  2022年   10篇
  2021年   25篇
  2020年   26篇
  2019年   38篇
  2018年   26篇
  2017年   29篇
  2016年   41篇
  2015年   50篇
  2014年   36篇
  2013年   63篇
  2012年   34篇
  2011年   38篇
  2010年   27篇
  2009年   30篇
  2008年   31篇
  2007年   39篇
  2006年   29篇
  2005年   38篇
  2004年   34篇
  2003年   28篇
  2002年   33篇
  2001年   32篇
  2000年   19篇
  1999年   19篇
  1998年   7篇
  1997年   2篇
  1996年   6篇
  1995年   3篇
  1994年   3篇
  1993年   2篇
  1992年   1篇
  1990年   1篇
排序方式: 共有809条查询结果,搜索用时 31 毫秒
1.
2.
认知障碍是指记忆、语言、理解和判断等一个或多个方面的功能障碍,包括轻度认知障碍和各种类型的痴呆症。痴呆症是认知障碍最严重的表现,是一种导致患者日常生活、社会交往和工作能力发生显著变化的综合征。阿尔茨海默病(AD)是最常见的痴呆症类型,其次是血管性痴呆(VD)和其他神经退行性痴呆[1]。已知年龄与认知功能的退化密切相关。  相似文献   
3.
The current evidence on the association of leukocyte telomere length (LTL) with age-related structural and cognitive changes in the brain is mixed. Herein conforming to PRISMA 2020 guidelines, we performed a systematic review and meta-analysis using data from 27 observational studies in non-demented individuals. We used effect size and p-value based meta-analysis methods considering marked heterogeneity among studies. We found that the longer LTL was associated with higher brain volume (β = 0.43, 95%CI: 0.36–0.50%, p = 0.008, N = 1102) and with higher global cognition (β = 0.01; 95%CI: 0.00–0.02, p = 0.03, N = 19609) by effect size based meta-analysis and with brain volume, hippocampal volume, global cognition, cognitive domains of attention/speed as well as executive functions by p-value based meta-analysis. No significant association of LTL with brain white matter hyperintensities was detected. Furthermore, the evidence strongly suggests a subgroup-specific canonical effect of telomeres, notably in older individuals and females. In conclusion, we provide meta-analytic evidence on the beneficial effect of telomeres on brain structure as well as cognition and advocate for a beneficial subgroup-specific effect that warrants further attention.  相似文献   
4.
Telomeric repeat‐containing RNA (TERRA) is closely involved in the regulation of telomere length, which plays critical roles in tumorigenesis. However, the biological significance of TERRA in hepatocellular carcinoma (HCC) remains largely unknown. In this study, we found that HCC cells show a frequent downregulation of TERRA and its positive regulator TTAGGG repeat binding factor‐1 (TRF1), whereas the negative regulator TTAGGG repeat binding factor‐1 (TRF2) was upregulated. We found that TERRA, TRF1, and TRF2 contributed to poor prognosis of HCC patients. Importantly, we found that the downregulation of TERRA significantly promoted HCC cell growth and metastasis in vitro and in vivo, whereas the upregulation of TERRA showed an opposite effect. Mechanistically, downregulation of TERRA significantly increased telomerase activity and promoted telomere elongation. Moreover, the inhibitory effects of TERRA overexpression on the growth and metastasis of HCC cells were reversed by treatment with TA‐65 that activates telomerase activity. In contrast, the protumor effect of TERRA downregulation was reversed by treatment with TMPyP4 that inhibits telomerase activity. Our findings reveal that TERRA plays a critical role in HCC cell growth and metastasis, indicating that TERRA is a potential therapeutic target for HCC.  相似文献   
5.
6.
 随着全球老龄化的到来,衰老及其相关疾病带来的健康问题日益严峻。血管老化包括血管结构和功能的改变,也是心血管疾病发生发展的重要因素,是机体衰老的一部分。目前科学家对血管老化机制的研究甚少,本文将从血管老化的分子机制和硫化氢的保护作用两个方面入手,综述了血管老化方面的最新进展。  相似文献   
7.
谢忠礼  翟振兴  轩丽勇 《中医学报》2016,(11):1726-1729
目的:观察加味四逆散对慢性疲劳综合征模型大鼠额叶、海马区神经元端粒长度及端粒酶活性的影响,探讨中医疏理气机法防治慢性疲劳综合征的神经端粒机制。方法:SD雌性1月龄大鼠100只,随机分为对照组、模型组、加味四逆散组、小柴胡汤组、柴胡加龙骨牡蛎汤组、怀牛膝组、四物汤组、黄芪建中汤组、人参组、帕罗西汀组,每组10只。采用慢性不可预见的中等强度应激刺激,造成动物的慢性疲劳状态。用酶联免疫吸附法研究端粒酶活性变化,用Southern Blotting法研究端粒长度变化。结果:1海马端粒酶活性变化:与对照组比较,除加味四逆散组外,其余各组均降低,且有统计学差异(P0.01);与模型组比较,除怀牛膝组和柴胡加龙骨牡蛎汤组外,其余各组均升高,且有统计学差异(P0.01)。2额叶端粒酶活性变化:与对照组比较,除加味四逆散组和小柴胡汤组外,其余各组均降低,且有统计学差异(P0.01);与模型组比较,除怀牛膝组和柴胡加龙骨牡蛎汤组外,其余各组均升高,且有统计学差异(P0.01)。3海马端粒长度变化:与对照组比较,除加味四逆散组外,其余各组端粒长度均缩短,且有统计学差异(P0.01);与模型组比较,除怀牛膝组和柴胡加龙骨牡蛎汤组外,其余各组端粒长度均延长,且有统计学差异(P0.01)。4额叶端粒长度:与对照组比较,除加味四逆散组外,其余各组端粒长度均缩短,且有统计学差异(P0.01);与模型组比较,除怀牛膝组和柴胡加龙骨牡蛎汤组外,其余各组端粒长度均延长,且有统计学差异(P0.01)。结论:慢性应激能诱发大鼠慢性疲劳状态,降低额叶区、海马区的端粒酶活性,缩短端粒长度。加味四逆散、小柴胡汤、四物汤、黄芪建中汤和人参可不同程度改善慢性应激大鼠的疲劳症状,其中以加味四逆散和小柴胡汤较优,其机制可能与调节额叶和海马区的端粒酶活性及保护端粒损伤有关。  相似文献   
8.
9.
Antigen-specific multifunctional T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α simultaneously after activation are important for the control of many infections. It is unclear if these CD8+ T cells are at an early or late stage of differentiation and whether telomere erosion restricts their replicative capacity. We developed a multi-parameter flow cytometric method for investigating the relationship between differentiation (CD45RA and CD27 surface phenotype), function (cytokine production) and replicative capacity (telomere length) in individual cytomegalovirus (CMV) antigen-specific CD8+ T cells. This involves surface and intracellular cell staining coupled to fluorescence in situ hybridization to detect telomeres (flow-FISH). The end-stage/senescent CD8+ CD45RA+ CD27 T-cell subset increases significantly during ageing and this is exaggerated in CMV immune-responsive subjects. However, these end-stage cells do not have the shortest telomeres, implicating additional non-telomere-related mechanisms in inducing their senescence. The telomere lengths in total and CMV (NLV)-specific CD8+ T cells in all four subsets defined by CD45RA and CD27 expression were significantly shorter in old compared with young individuals in both a Caucasian and an Asian cohort. Following stimulation by anti-CD3 or NLV peptide, similar proportions of triple-cytokine-producing cells are found in CD8+ T cells at all stages of differentiation in both age groups. Furthermore, these multi-functional cells had intermediate telomere lengths compared with cells producing only one or two cytokines after activation. Therefore, global and CMV (NLV)-specific CD8+ T cells that secrete interferon-γ, interleukin-2 and tumour necrosis factor-α are at an intermediate stage of differentiation and are not restricted by excessive telomere erosion.  相似文献   
10.
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