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101.
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
102.
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
103.
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
104.
105.
106.
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
107.
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
108.
Breast cancer is believed to be driven by epigenetic regulation of genes implicated in cell proliferation, survival, and differentiation. Recently, aberrant N6-methyladenosine (m6A) decorations turned up as crucial epigenetic regulator for malignant breast cancer, which may serve as new targets for breast cancer treatment. Here we briefly outline the functions of m6A and its regulatory proteins, including m6A “writers,” “readers,” and “erasers” on RNA life fate, recapitulate the latest breakthroughs in understanding m6A modification and its regulatory proteins, and the underlying molecular mechanisms that contribute to the carcinogenesis and the progression of breast cancer, so as to provide potential epigenetic targets for diagnosis, treatment and prognosis in breast cancer. 相似文献
109.
目的:探讨5-氮杂-2’-脱氧胞苷/曲古抑菌素A(5-Aza/TSA)介导的DNA去甲基化/组蛋白乙酰化处理对B细胞来源的非霍奇金淋巴瘤B细胞表型的影响。方法:构建含有G418抗性的CD19特异性启动e GFP表达载体,转染霍奇金(阴性对照)和非霍奇金淋巴瘤细胞,并筛选目的序列稳定整合的克隆,比较CD19启动子在2组细胞中的活性。流式细胞术检测5-Aza/TSA处理对2组细胞GFP表达水平的影响。分离Eμ-myc转基因小鼠非霍奇金淋巴瘤原代细胞并鉴定其B细胞表型,通过流式细胞术检测5-Aza/TSA对其B细胞表面抗原CD19等表达水平的影响。结果:5-Aza/TSA表观遗传处理能够降低人非霍奇金淋巴瘤细胞中外源性CD19启动子的转录活性,并沉默小鼠原代非霍奇金淋巴瘤细胞表面B细胞特异性抗原的表达。结论:DNA甲基化和组蛋白去乙酰化对人类及小鼠B细胞来源的非霍奇金淋巴瘤B细胞表型稳定有重要作用。 相似文献
110.
异硫氰酸苯己酯对Molt-4细胞组蛋白甲基化、乙酰化调控的实验研究 总被引:1,自引:0,他引:1
目的 研究异硫氰酸苯己酯(PHI)在体外对淋巴细胞白血病Molt-4细胞系的作用,观察PHI对Molt-4细胞组蛋白甲基化、乙酰化调控的影响。方法 采用MTT法、克隆抑制实验观察PHI对Molt-4细胞增殖的影响;采用流式细胞术检测PHI诱导细胞凋亡和对细胞周期的影响;用Western blot法观察PHI作用后细胞的组蛋白乙酰化酶、组蛋白甲基化及乙酰化状态的变化。结果 PHI可上调Molt-4细胞组蛋白乙酰化酶P300/CBP水平,显著提高组蛋白H3、H4乙酰化及H3K4甲基化水平,抑制组蛋白甲基化H3K9表达,阻滞细胞于G0/G1期,并诱导细胞凋亡。结论 PHI可能是一种组蛋白去乙酰化酶抑制剂,同时能调控组蛋白甲基化,影响其表观遗传学,可能作为新的抗白血病治疗药物。 相似文献