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101.
WenQian Zhang Wei Sun Yuan Qin CangHao Wu Liang He Ting Zhang Liang Shao Hao Zhang Ping Zhang 《Journal of cellular and molecular medicine》2019,23(8):4933-4944
Epigenetic dysregulation plays an important role in cancer. Histone demethylation is a well‐known mechanism of epigenetic regulation that promotes or inhibits tumourigenesis in various malignant tumours. However, the pathogenic role of histone demethylation modifiers in papillary thyroid cancer (PTC), which has a high incidence of early lymphatic metastasis, is largely unknown. Here, we detected the expression of common histone demethylation modifiers and found that the histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) demethylase KDM1A (or lysine demethylase 1A) is frequently overexpressed in PTC tissues and cell lines. High KDM1A expression correlated positively with age <55 years and lymph node metastasis in patients with PTC. Moreover, KDM1A was required for PTC cell migration and invasion. KDM1A knockdown inhibited the migration and invasive abilities of PTC cells both in vitro and in vivo. We also identified tissue inhibitor of metalloproteinase 1 (TIMP1) as a key KDM1A target gene. KDM1A activated matrix metalloproteinase 9 (MMP9) through epigenetic repression of TIMP1 expression by demethylating H3K4me2 at the TIMP1 promoter region. Rescue experiments clarified these findings. Altogether, we have uncovered a new mechanism of KDM1A repression of TIMP1 in PTC and suggest that KDM1A may be a promising therapeutic target in PTC. 相似文献
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Yen-Sung Huang Hsin-Yi Hsieh Hsiu-Ming Shih Huey-Kang Sytwu Chia-Chao Wu 《Biochemical and biophysical research communications》2014
Membranous nephropathy (MN), a type of glomerular nephritis, is the most common cause of nephrotic syndrome in human adults. Changes in gene expression as a result of epigenetic dysregulation through long noncoding RNAs (lncRNAs) are increasingly being recognized as important factors in disease. Using an experimental MN mouse model, we identify the first dysregulated lncRNAs, Xist and NEAT1, whose levels are significantly upregulated in both tubular epithelial and glomerular cells. MN is also often characterized by glomerular podocyte injury. Treatment of a mouse podocyte cell line with lipopolysaccharides to induce injury resulted in the stable elevation of Xist, but not NEAT1 levels. In mice, the observed changes in Xist levels are specific: Xist can be effectively detected in urine, with a strong correlation to disease severity, but not serum in MN samples. We find that regulation of Xist may be controlled by post-translational modifications. H3K27me3 levels are significantly downregulated in mouse MN kidney, where chromatin immunoprecipitation experiments also showed decreased H3K27me3 at Xist promoter regions. Finally, we show that our findings in mice can be extended to human clinical samples. Urinary Xist is significantly elevated in urine samples from patients with different types of glomerular nephritis, including MN, compared to normal counterparts. Together, our results suggest that a reduction of H3K27me3 at Xist promoter regions leads to elevated levels of urinary Xist, which may be used as a biomarker to detect MN. 相似文献
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Different cell types within a single organism are generally distinguished by strikingly different patterns of gene expression, which are dynamic throughout development and adult life. Distal enhancer elements are key drivers of spatiotemporal specificity in gene regulation. Often located tens of kilobases from their target promoters and functioning in an orientation-independent manner, the identification of bona fide enhancers has proved a formidable challenge. With the development of ChIP-seq, global cataloging of putative enhancers has become feasible. Here, we review the current understanding of the chromatin landscape at enhancers and how these chromatin features enable robust identification of tissue-specific enhancers. 相似文献
107.
PI3K/AKT信号通路调控Myogenin和MCK基因的表达 总被引:1,自引:0,他引:1
骨骼肌分化过程受多个信号通路调控, PI3K/AKT信号通路是其中最重要的信号转导通路之一。PI3K/AKT信号通路可以调控骨骼肌分化, 但在染色质水平上的调控机制还不是很清楚。文章以小鼠成肌细胞(C2C12)为研究材料, 采用免疫印迹、染色质免疫共沉淀(Chromatin immunoprecipitation, ChIP)、定量PCR (Q-PCR)的方法研究PI3K/AKT信号通路调控Myogenin和MCK基因的表达。研究发现, C2C12细胞分化过程中添加PI3K/AKT信号通路激活剂处理24 h, Myogenin和MCK蛋白表达水平显著升高, 组蛋白H3K27me3去甲基化酶UTX的表达也升高, H3K27me3在Myogenin基因启动子区和MCK基因启动子及增强子区的富集与对照组相比显著降低。用PI3K/AKT信号通路抑制剂处理, 结果相反。因此, PI3K/AKT信号通路可能通过调控组蛋白去甲基化酶UTX的表达活性改变靶基因的H3K27me3的富集进而调控骨骼肌分化。 相似文献
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The impact of the 2003 summer heat wave and the 2005 late cold wave on the phytoplankton in the north-eastern English Channel 总被引:1,自引:0,他引:1
The phytoplankton composition was investigated at two fixed stations in the north-eastern English Channel from November 1997 to December 2005. The warmest temperatures in European historical records were recorded in August 2003. This event was associated with an exceptional abundance peak of the dinoflagellates Akashiwo sanguinea (9600 cells L(-1)) and Ceratium fusus. The lowest February temperatures for the 1998-2005 period were recorded in 2005, coinciding with the absence, for the first time in recent decades, of the spring bloom of Phaeocystis globosa. The 'de-eutrophication', mainly the reduction of river nutrient loads, is progressively reducing the magnitude of the Phaeocystis blooms. Exceptionally in 2005, the colder temperatures increased water column mixing, favouring the dominance of tychoplanktonic diatoms until early March (pre-bloom period). The delay in spring stratification, lower light availability due to turbidity (resuspended sediment) and organic matter, and competition with tychoplanktonic diatoms contributed to retard the timing of the spring phytoplankton bloom and disadvantage the development of Phaeocystis. The summer 2003 European heat wave is expected to have had little influence on total annual primary production, because it occurred at mid-summer, the period of lowest annual phytoplankton abundance. However, the anomalous weather in the second half of winter 2005 did affect the annual primary production. 相似文献
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