全文获取类型
收费全文 | 941篇 |
免费 | 63篇 |
国内免费 | 54篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 34篇 |
妇产科学 | 34篇 |
基础医学 | 202篇 |
口腔科学 | 10篇 |
临床医学 | 29篇 |
内科学 | 186篇 |
皮肤病学 | 9篇 |
神经病学 | 134篇 |
特种医学 | 7篇 |
外科学 | 70篇 |
综合类 | 46篇 |
预防医学 | 43篇 |
眼科学 | 12篇 |
药学 | 85篇 |
中国医学 | 5篇 |
肿瘤学 | 147篇 |
出版年
2023年 | 20篇 |
2022年 | 56篇 |
2021年 | 74篇 |
2020年 | 51篇 |
2019年 | 47篇 |
2018年 | 76篇 |
2017年 | 57篇 |
2016年 | 63篇 |
2015年 | 74篇 |
2014年 | 102篇 |
2013年 | 90篇 |
2012年 | 58篇 |
2011年 | 98篇 |
2010年 | 44篇 |
2009年 | 42篇 |
2008年 | 31篇 |
2007年 | 25篇 |
2006年 | 31篇 |
2005年 | 5篇 |
2004年 | 10篇 |
2003年 | 3篇 |
2000年 | 1篇 |
排序方式: 共有1058条查询结果,搜索用时 15 毫秒
91.
92.
Hitomi Fujishiro Satomi Okugaki Saori Yasumitsu Shuichi Enomoto Seiichiro Himeno 《Toxicology and applied pharmacology》2009,241(2):101-125
The Zrt/Irt-related protein 8 (ZIP8) encoded by slc39a8 is now emerging as an important zinc transporter involved in cellular cadmium incorporation. We have previously shown that mRNA and protein levels of ZIP8 were decreased in cadmium-resistant metallothionein-null (A7) cells, leading to a decrease in cadmium accumulation. However, the mechanism by which ZIP8 expression is suppressed in these cells remains to be elucidated. In the present study, we investigated the possibility that epigenetic silencing of the slc39a8 gene by DNA hypermethylation is involved in the down-regulation of ZIP8 expression. A7 cells showed a higher mRNA level of DNA methyltransferase 3b than parental cells. Hypermethylation of the CpG island of the slc39a8 gene was detected in A7 cells. Treatment of A7 cells with 5-aza-deoxycytidine, an inhibitor of DNA methyltransferase, caused demethylation of the CpG island of the slc39a8 gene and enhancement of mRNA and protein levels of ZIP8. In response to the recovery of ZIP8 expression, A7 cells treated with 5-aza-deoxycytidine showed an increase in cadmium accumulation and consequently an increase in sensitivity to cadmium. These results suggest that epigenetic silencing of the slc39a8 gene by DNA hypermethylation plays an important role in the down-regulation of ZIP8 in cadmium-resistant metallothionein-null cells. 相似文献
93.
94.
J?rg D?tsch Christian Plank Kerstin Amann Julie Ingelfinger 《Journal of molecular medicine (Berlin, Germany)》2009,87(9):841-848
Large epidemiological studies suggest a clear relation between low birth weight and adverse renal outcomes evident as early
as during childhood. Such adverse outcomes may include glomerular disease, hypertension, and renal failure. Data from autopsy
material and from experimental models suggest that reduction in nephron number via diminished nephrogenesis may be a major
mechanism, and factors that lead to this reduction are incompletely elucidated. Other mechanisms appear to be renal (e.g.,
via the intrarenal renin–angiotensin–aldosterone system) and nonrenal (e.g. changes in endothelial function). It also appears
likely that the outcomes of fetal programming may be influenced postnatally, for example, by the amount of nutrients given
at critical times. 相似文献
95.
随着人类对肿瘤研究的日益深入,许多学者已经清楚地认识到,肿瘤的发生、发展不仅与细胞内基因突变、缺失等因核苷酸序列改变所导致的遗传调控紊乱有关,还与表观遗传调控异常有着密切的联系[1].所谓表观遗传,是指通过DNA甲基化、组蛋白乙酰化和甲基化、染色质构型变化等所导致的在基因表达水平的改变.它只影响基因的转录活性而不影响核苷酸序列的改变[2].其中,DNA甲基化作为常见的表观遗传学修饰模式,在哺乳动物基因表达调控中起着重要的作用.异常甲基化可导致癌基冈的活化、非必需重复序列的转录、抑癌基因及DNA修复基因的沉默等,并能以半保留的方式高保真地传递到子代细胞的基岗组中,最终引发肿瘤[1]. 相似文献
96.
Inhibition of histone deacetylation protects wildtype but not gelsolin-deficient mice from ischemic brain injury 总被引:1,自引:0,他引:1
Yildirim F Gertz K Kronenberg G Harms C Fink KB Meisel A Endres M 《Experimental neurology》2008,210(2):531-542
Acetylation/deactylation of histones is an important mechanism to regulate gene expression and chromatin remodeling. We have previously demonstrated that the HDAC inhibitor trichostatin A (TSA) protects cortical neurons from oxygen/glucose deprivation in vitro which is mediated--at least in part--via the up regulation of gelsolin expression. Here, we demonstrate that TSA treatment dose-dependently enhances histone acetylation in brains of wildtype mice as evidenced by immunoblots of total brain lysates and immunocytochemical staining. Along with increased histone acetylation dose-dependent up regulation of gelsolin protein was observed. Levels of filamentous actin were largely decreased by TSA pre-treatment in brain of wildtype but not gelsolin-deficient mice. When exposed to 1 h filamentous occlusion of the middle cerebral artery followed by reperfusion TSA pre-treated wildtype mice developed significantly smaller cerebral lesion volumes and tended to have improved neurological deficit scores compared to vehicle-treated mice. These protective effects could not be explained by apparent changes in physiological parameters. In contrast to wildtype mice, TSA pre-treatment did not protect gelsolin-deficient mice against MCAo/reperfusion suggesting that enhanced gelsolin expression is an important mechanism by which TSA protects against ischemic brain injury. Our results suggest that HDAC inhibitors such as TSA are a promising therapeutic strategy for reducing brain injury following cerebral ischemia. 相似文献
97.
98.
99.
膀胱肿瘤是我国最常见的泌尿外科肿瘤,无论其发病率或死亡率均占首位.DNA异常甲基化是肿瘤发生、发展过程中常见的表观遗传学改变,在膀胱肿瘤中扮演着重要角色.近年来,研究者对膀胱肿瘤DNA异常甲基化进行了大量的研究,为开辟膀胱肿瘤筛查、诊断和治疗的新途径奠定了实验基础. 相似文献
100.
Steven G. Gray 《CNS Neuroscience & Therapeutics》2010,16(6):348-361
Huntington's disease is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite the identification of the causative element, an expanded toxic polyglutamine tract in the mutant Huntingtin protein, treatment options for patients with this disease remain limited. In the following review I assess the current evidence suggesting that a family of important regulatory proteins known as histone deacetylases may be an important therapeutic target in the treatment of this disease. 相似文献