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1.
《Molecular therapy》2022,30(12):3714-3728
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《Clinical breast cancer》2022,22(6):507-514
Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.  相似文献   
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Initially identified in Drosophila, the Hippo signaling pathway regulates how cells respond to their environment by controlling proliferation, migration and differentiation. Many recent studies have focused on characterizing Hippo pathway function and regulation in mammalian cells. Here, we present a brief overview of the major components of the Hippo pathway, as well as their regulation and function. We comprehensively review the studies that have contributed to our understanding of the Hippo pathway in the function of the peripheral nervous system and in peripheral nerve diseases. Finally, we discuss innovative approaches that aim to modulate Hippo pathway components in diseases of the peripheral nervous system.  相似文献   
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目的探讨非小细胞肺癌(NSCLC)中miR-200a与Yes相关蛋白1(YAP1)表达量在癌组织和癌旁组织的相关性及其临床病理意义。方法回顾性选取259例非小细胞肺癌患者术后切除的肿瘤组织及癌旁组织为本次研究对象,采用RT-PCR方法检测并比较患者的miR-200a与YAP1表达量在癌组织和癌旁组织的相关性及其临床病理意义。结果所选患者中miR-200a及YAP1在非小细胞肺癌中表达量显示,miR-200a与YAP1的表达量在病理类型、浸润深度、肿瘤分级、肿瘤数目中的比较,差异无统计学意义(P>0.05)。miR-200a与YAP1的表达量在肿瘤分化程度、淋巴结转移的比较中,差异有统计学意义(P<0.05)。所选患者中miR-200a、YAP1在非小细胞肺癌组织表达量比癌旁组织较高,其中,YAP1的非小细胞肺癌组织表达量水平明显高于miR-200a的表达量水平,差异有统计学意义(P<0.05)。miR-200a、YAP1对非小细胞肺癌ROC曲线显示,miR-200a的ROC曲线下面积0.689比YAP1的0.666大,差异有统计学意义(P<0.05)。结论 miR-200a、YAP1表达量水平与非小细胞肺癌临床病理严重程度呈正相关,对非小细胞肺癌诊断有一定预测价值。  相似文献   
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Urothelial carcinoma of bladder (UCB) is a common urological malignancy in the world, but its progression mechanism remains unclear. MiR-612 was found as an anti-tumor factor in multiple types of cancer, while few studies have revealed its functions in UCB cells. Based on this, UCB cells such as HTB-9 and HTB-4, and normal urothelial of bladder cells such as SV-Huc1, were used as subjects in this study. Western blot, qRTPCR, CCK-8 assay and transwell assay were used to assess functions of miR-612 in UCB cells. The database, miRWalk, was used to search for potential targets of miR-612, and dual-luciferase reporter assay was used to verify the accuracy of the forecasting results. Besides, PMEPA1 overexpressed vector and miR-612 mimics were co-transfected into HTB-4 to observe the regulation mechanism of miR-612. It was found that miR-612 was significantly downregulated in HTB-9 and HTB-4 cells rather than in SV-Huc1 cells, and overexpressed miR-612 reduced the proliferation and invasion of HTB-4 cells. The expression level of YAP1 was negatively related with miR-612 while LATS1 was positively related with miR-612. Besides, the results of miRWalk and dual-luciferase reporter assay indicated that PMEPA1 was a target of miR-612, and overexpression of PMEPA1 could reverse the effects of miR-612 on UCB including weakened proliferation and invasion abilities, low expression level of YAP1 and high expression level of LATS1. Therefore, this study suggests that miR-612 inhibits the proliferation and invasion of urothelial carcinoma of bladder cells through activating Hippo pathway via targeting PMEPA1.  相似文献   
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目的探讨miR-146b在高糖环境下对肾小球系膜细胞的作用。方法构建高糖培养环境,实时荧光定量PCR(qRT-PCR)检测miR-146b在大鼠肾小管上皮细胞(NRK-52E)、足细胞(podocyte)及肾小球系膜细胞(HBZY-1)中的表达水平;western blot分析过表达/敲减miR-146b前后,HBZY-1细胞中YAP及磷酸化YAP(p-YAP)蛋白的表达水平;细胞免疫荧光法检测YAP蛋白的表达情况。结果体外经高糖刺激后,HBZY-1细胞中miR-146b的表达水平(2.197±0.166)明显升高(t=7.215,P0.01)。western blot结果显示,高糖组YAP蛋白(0.753±0.008)的表达水平升高(t=32.17,P0.001),p-YAP蛋白(0.372±0.005)的表达水平降低(t=39.56,P0.001);免疫荧光结果显示,高糖组YAP蛋白荧光强度(53.620±4.229)明显升高(t=5.410,P0.01)。过表达miR-146b后,western blot结果显示,YAP蛋白(0.883±0.005)表达上调(t=10.71,P0.001),而p-YAP蛋白(0.606±0.006)表达下调(t=44.16,P0.001);免疫荧光结果显示,YAP荧光强度(25.70±1.589)增强(t=10.45,P0.001)。敲减miR-146b后,western blot结果显示,YAP蛋白(0.706±0.002)表达下调(t=22.15,P0.001),p-YAP蛋白(0.774±0.003)表达上调(t=25.61,P0.001);免疫荧光结果显示,YAP荧光强度(8.900±1.022)减弱(t=11.56,P0.001)。结论 miR-146b在高糖刺激的HBZY-1细胞中表达上调,可能通过调控YAP信号参与肾细胞损伤。  相似文献   
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Cell competition is a biological process by which unfit cells are eliminated from “cell society.” We previously showed that cultured mammalian epithelial Madin‐Darby canine kidney (MDCK) cells expressing constitutively active YAP were eliminated by apical extrusion when surrounded by “normal” MDCK cells. However, the molecular mechanism underlying the elimination of active YAP‐expressing cells was unknown. Here, we used high‐throughput chemical compound screening to identify cyclooxygenase‐2 (COX‐2) as a key molecule triggering cell competition. Our work shows that COX‐2‐mediated PGE2 secretion engages its receptor EP2 on abnormal and nearby normal cells. This engagement of EP2 triggers downstream signaling via an adenylyl cyclase‐cyclic AMP‐PKA pathway that, in the presence of active YAP, induces E‐cadherin internalization leading to apical extrusion. Thus, COX‐2‐induced PGE2 appears a warning signal to both abnormal and surrounding normal cells to drive cell competition.  相似文献   
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目的::研究YAP蛋白在肺腺癌中的表达及其意义。方法:采取免疫组织化学方法检测90例肺腺癌和癌旁正常肺组织YAP表达情况,并进行统计分析。结果:YAP蛋白在肺腺癌中表达明显高于癌旁正常肺组织(P<0.05),各期肺腺癌组织中 YAP 蛋白表达无显著差异(P>0.05)。结论:YAP 蛋白在人肺腺癌组织中表达明显增加,可能参与肺腺癌的发生与发展。  相似文献   
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