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1.
Deletion of 3p13 has been reported from about 20% of prostate cancers. The clinical significance of this alteration and the tumour suppressor gene(s) driving the deletion remain to be identified. We have mapped the 3p13 deletion locus using SNP array analysis and performed fluorescence in situ hybridization (FISH) analysis to search for associations between 3p13 deletion, prostate cancer phenotype and patient prognosis in a tissue microarray containing more than 3200 prostate cancers. SNP array analysis of 72 prostate cancers revealed a small deletion at 3p13 in 14 (19%) of the tumours, including the putative tumour suppressors FOXP1, RYBP and SHQ1. FISH analysis using FOXP1‐specific probes revealed deletions in 16.5% and translocations in 1.2% of 1828 interpretable cancers. 3p13 deletions were linked to adverse features of prostate cancer, including advanced stage (p < 0.0001), high Gleason grade (p = 0.0125), and early PSA recurrence (p = 0.0015). In addition, 3p13 deletions were linked to ERG+ cancers and to PTEN deletions (p < 0.0001 each). A subset analysis of ERG+ tumours revealed that 3p13 deletions occurred independently from PTEN deletions (p = 0.3126), identifying tumours with 3p13 deletion as a distinct molecular subset of ERG+ cancers. mRNA expression analysis confirmed that all 3p13 genes were down regulated by the deletion. Ectopic over‐expression of FOXP1, RYBP and SHQ1 resulted in decreased colony‐formation capabilities, corroborating a tumour suppressor function for all three genes. In summary, our data show that deletion of 3p13 defines a distinct and aggressive molecular subset of ERG+ prostate cancers, which is possibly driven by inactivation of multiple tumour suppressors. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.  相似文献   
2.
[摘要] 目的:构建抑癌基因PTEN真核表达载体pEGFP-PTEN,并观察其在人舌鳞癌scc-4细胞系中的表达,为舌鳞癌的基因治疗提供理论依据。方法:提取人HeLa细胞总RNA,采用RT-PCR法获取PTEN全基因,克隆至pMD18-T载体,经EcoRⅠ和XhoⅠ双酶切后与真核表达载体pEGFP-N1连接,构建pEGFP-PTEN重组质粒。双酶切及测序鉴定后,经脂质体介导转染至体外培养的人舌鳞癌SCC-4细胞系,荧光显微镜观察绿色荧光蛋白在细胞内的表达;Western blotting法检测细胞内PTEN蛋白的表达。结果:pEGFP-PTEN重组质粒双酶切,克隆的目的基因片段约为1 200 bp,测序结果与GenBank上PTEN序列完全一致;荧光显微镜下观察到pEGFP-PTEN在SCC-4细胞系中成功表达;Western blotting结果,转染组PTEN蛋白表达强度为1.07±0.15,与空转染组(0.62±0.11)和未转染组(0.57±0.08)比较差异有统计学意义(P<0.05)。结论:成功构建pEGFP-PTEN重组真核表达载体,该载体能在人舌鳞癌SCC-4细胞系中表达。  相似文献   
3.
Ming M  He YY 《Cancer letters》2012,319(2):125-129
The ability of DNA repair in a cell is vital to its genomic integrity and thus to the normal functioning of an organism. Phosphatase and tensin homolog (PTEN) is a well-established tumor suppressor gene that induces apoptosis and controls cell growth by inhibiting the PI3K/AKT pathway. In various human cancers, PTEN is frequently found to be mutated, deleted, or epigenetically silenced. Recent new findings have demonstrated that PTEN also plays a critical role in DNA damage repair and DNA damage response. This review summarizes the recent progress in the function of PTEN in DNA damage repair, especially in double strand break repair and nucleotide excision repair. In addition, we will discuss the role of PTEN in DNA damage response through its interaction with the Chk1 and p53 pathways. We will focus on the newly discovered mechanisms and the potential implications in cancer prevention and therapeutic intervention.  相似文献   
4.
Das AB  Loying P  Bose B 《Cancer letters》2012,318(2):189-198
Human oncofetal protein Cripto-1 (CR-1) is overexpressed in many types of cancers. CR-1 binds to cell surface Glypican-1 to activate Erk1/2 MAPK and Akt pathways leading to cell proliferation. However, we show that treatment with recombinant CR-1 reduces proliferation of HeLa cells by increasing the doubling time without triggering cell death or cell cycle arrest. Using a comparative study with U-87 MG cells, we show that the pro-proliferative pathway of CR-1 is not effective in HeLa cells due to lower expression of Glypican-1. Further we show that treatment with recombinant CR-1 increases PTEN in HeLa cells leading to downregulation of PI3K/Akt pathway. The anti-proliferative effect gets potentiated when the pro-proliferative pathway is blocked.  相似文献   
5.
6.
Male breast cancer (MBC) is unusual, especially in young adults. Most cases of MBC as a secondary malignancy relate to the previous treatment with ionizing radiation. MBC can be associated with mutations in hereditary cancer predisposition syndrome genes (i.e., BRCA2); however, no such association has been reported in patients with Cowden syndrome (involving the phosphatase and tensin homolog [PTEN] gene). We describe a patient with Cowden syndrome who was initially diagnosed with B‐cell lymphoblastic lymphoma at the age of 7 years, then MBC at the age of 31 years, and never received radiation therapy.  相似文献   
7.
目的:探讨胃癌组织miR-155的表达水平及其临床意义。方法:收集手术切除的胃癌标本116例,采用实时荧光定量反转录聚合酶链反应(qRT-PCR)检测癌及癌旁组织miR-155的表达水平,分析其与临床病理的关系及对临床预后的影响。采用免疫组织化学法检测癌组织中PTEN的表达,分析其表达与miR-155的相关性。结果:胃癌组织miR-155表达高于配对癌旁组织,差异有统计学意义(P0.001);miR-155高表达与肿瘤TNM分期、侵犯层次、淋巴结转移有关(P0.05)。K-M曲线分析表明,miR-155高表达预示着较低的3年无病进展率(P0.001)及总生存率(P0.001)。PTEN表达与miR-155负相关,miR-155高表达患者PTEN表达低(P0.001)。结论:miR-155与胃癌发生发展密切相关,可能是胃癌潜在的临床诊断及预后指标。  相似文献   
8.
9.
翟丽娜  翁翔  黄强 《中国肿瘤》2015,24(6):517-523
[目的]探讨苦参碱体外诱导非霍奇金淋巴瘤raji细胞增殖与凋亡的机制是否与PI3K/AKt信号通路有关.[方法]M TT法检测苦参碱作用后raji细胞的增殖抑制率;流式细胞仪检测苦参碱作用后raii细胞的细胞周期的变化;RT-PCR检测苦参碱作用后PTEN、AKt、caspase3等mRNA水平的变化;Western blot检测PTEN、pBad、Bad、pAKt、AKt、caspase3等蛋白的表达.[结果]苦参碱可抑制raji细胞的增殖,随着药物浓度的提高和作用时问的延长,细胞的增殖抑制率逐渐升高,与对照组比较,差异均有显著(P<0.001);苦参碱诱导raii细胞周期停滞于G1期(P<0.05);苦参碱可通过磷酸化AKt来上调PTEN的表达,引起Bad、p21、p27等的变化,与对照组分别比较表达水平差异均有统计学意义(P<0.05),最终诱导caspase家族级联反应,引发肿瘤细胞的凋亡.[结论]苦参碱可通过PI3K/AKt信号通路抑制非霍奇金淋巴瘤raii细胞的增殖,诱导raji细胞凋亡.  相似文献   
10.
目的 探讨野生型第10 号染色体缺失的磷酸酶张力蛋白同源物基因(PTEN)过表达对体外活化肝星状细胞(HSC)内钙离子浓度的影响。方法 体外培养活化大鼠肝星状细胞系(HSC-T6),利用腺病毒载体,将野生型PTEN 基因转染活化HSC ;Western blot 及实时荧光定量聚合酶链反应(qrt-PCR)检测HSC 的PTEN 蛋白及mRNA 表达;采用钙离子荧光探针Rhod-2/AM,于激光扫描共聚焦显微镜下检测HSC 内钙离子浓度变化。实验分组:① Control 组:腺病毒转染时以DMEM 代替病毒液;② Ad-GFP 组:转染表达绿色荧光蛋白(GFP)的对照空病毒Ad-GFP ;③ Ad-PTEN 组:转染携带野生型PTEN 基因并表达GFP 的重组腺病毒Ad-PTEN。结果 野生型PTEN 在活化大鼠HSC 大量表达,3 组HSC 内钙离子浓度比较,差异有统计学意义(P <0.05),Ad-PTEN 组HSC 内钙离子浓度(251.60±90.88)低于Control 组(1 953.95±132.99)及Ad-GFP 组(1 937.57±115.17),而Control 组与Ad-GFP 组之间HSC 内钙离子浓度比较,差异无统计学意义(P >0.05)。结论 野生型PTEN 过表达可降低体外活化大鼠HSC 内钙离子浓度。  相似文献   
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