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161.
Masatoshi Kudo Peter R. Galle Josep M. Llovet Richard S. Finn Arndt Vogel Kenta Motomura Eric Assenat Philippe Merle Giovanni Brandi Bruno Daniele Takuji Okusaka Jií Tomek Christophe Borg Vincenzo Dadduzio Manabu Morimoto Marc Pracht Min‐Hua Jen Nora Drove Ubreva Ryan C. Widau Kenta Shinozaki Reigetsu Yoshikawa Andrew X. Zhu 《Liver international》2020,40(8):2008-2020
162.
Sophie Paquet‐Fifield Nicole C Harris Sally Roufail Debra J Turner Yinan Yuan You‐Fang Zhang Stephen B Fox Margaret L Hibbs Jennifer L Wilkinson‐Berka Richard A Williams Steven A Stacker Marc G Achen 《The Journal of pathology》2016,239(2):152-161
Leakage of fluid from blood vessels, leading to oedema, is a key feature of many diseases including hyperoxic acute lung injury (HALI), which can occur when patients are ventilated with high concentrations of oxygen (hyperoxia). The molecular mechanisms driving vascular leak and oedema in HALI are poorly understood. VEGF‐D is a protein that promotes blood vessel leak and oedema when overexpressed in tissues, but the role of endogenous VEGF‐D in pathological oedema was unknown. To address these issues, we exposed Vegfd‐deficient mice to hyperoxia. The resulting pulmonary oedema in Vegfd‐deficient mice was substantially reduced compared to wild‐type, as was the protein content of bronchoalveolar lavage fluid, consistent with reduced vascular leak. Vegf‐d and its receptor Vegfr‐3 were more highly expressed in lungs of hyperoxic, versus normoxic, wild‐type mice, indicating that components of the Vegf‐d signalling pathway are up‐regulated in hyperoxia. Importantly, VEGF‐D and its receptors were co‐localized on blood vessels in clinical samples of human lungs exposed to hyperoxia; hence, VEGF‐D may act directly on blood vessels to promote fluid leak. Our studies show that Vegf‐d promotes oedema in response to hyperoxia in mice and support the hypothesis that VEGF‐D signalling promotes vascular leak in human HALI. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. 相似文献
163.
目的:分析阿帕替尼(apatinib,YN968D1)单药治疗晚期恶性肿瘤的疗效及不良反应。方法:检索Embase、PubMed、中国知网数据库,使用RStudio-3.5.1对纳入资料进行累积率的统计分析。结果:共检出文献1 260篇。根据纳入及排除标准,最终纳入194篇,包括118篇中文文献和76篇英文文献,总病例数为6 740例。结果显示,阿帕替尼单药治疗晚期胃癌、肺癌、乳腺癌、大肠癌、肉瘤的6个月PFS累积生存率分别为15%、26%、31%、24%、50%;单药治疗晚期肺癌、乳腺癌、大肠癌、肉瘤的12个月OS累积生存率分别为27%、38%、30%、45%。阿帕替尼常见不良反应有高血压、手足综合征和蛋白尿,累积发生率分别为39%、32%、28%。结论:阿帕替尼用于晚期恶性肿瘤的二线及以上治疗,具有客观有效性及安全性。 相似文献
164.
真菌非核糖体肽(nonribosomal peptides, NRPs)是一类重要的次级代谢产物,其中不乏结构和功能特殊、可作药用的化合物。本文介绍了组成非核糖体合成酶(nonribosomal peptide synthases, NRPSs)各结构域的功能,综述了已有报道的两种单模块非核糖体合成酶,即仅含有腺苷化结构域(adenylation domain, A结构域)、巯基化结构域(thiolation domain, T结构域)、硫酯酶结构域(thioesterase domain, TE结构域)的NRPSs:A-T-TE和仅含有腺苷化结构域、巯基化结构域、一个还原酶结构域(reductase domain, R结构域)的NRPSs:A-T-R的生物合成产物,并结合生物信息学分析推测了第3种含有腺苷化结构域、巯基化结构域、两个还原酶结构域的单模块NRPSs:A-T-R-R可能合成的产物结构。 相似文献
165.
Ting PENG ;Jian-rui WU ;Lin-jiang TONG ;Meng-yuan LI ;Fang CHEN ;Yi-xin LENG ;Rong QU ;Kun HAN ;Yi SU ;Yi CHEN ;Wen-hu DUAN ;Hua XIE ;Jian DING 《Acta pharmacologica Sinica》2014,35(7):916-928
Aim: 7,8-Dihydroxy-4-(3-hydroxy-4-methoxyphenyl)-2H-chromen-2-one (DW532) is one of simplified analogues of hematoxylin that has shown broad-spectrum inhibition on tyrosine kinases and in vitro anti-cancer activities. The aim of this study was to identify DW532 as a agent targeting both kinases and tubulin, and to investigate its anti-cancer and anti-angiogenesis activities. Methods: In vitro tyrosine kinases activity was examined with ELISA, and tyrosine kinases activity in cells was evaluated with Western blot analysis. Tubulin turbidity assay, surface plasmon resonance and immunofluorescence technique were used to characterize the tubulin inhibitory activity. Cell proliferation was examined with SRB assay, and cell apoptosis and cell cycle distribution were analyzed with Annexin-V/PI staining and flow cytometry. Tube formation, aortic ring and chick chorioallantoic membrane assays were used to evaluate the anti-angiogenesis efficacy. Results: DW532 inhibited EGFR and VEGFR2 in vitro kinase activity (the ICso values were 4.9 and 5.5 pmol/L, respectively), and suppressed their downstream signaling. DW532 dose-dependently inhibited tubulin polymerization via direct binding to tubulin, thus disrupting the mitotic spindle assembly and leading to abnormal cell division. In a panel of human cancer cells, DW532 (1 and 10 pmol/L) induced G2/M phase arrest and cell apoptosis, which subsequently resulted in cytotoxicity. Knockdown of BubR1 or Mpsl, the two core proteins of the spindle assembly checkpoint dramatically decreased DW532-induced cell cycle arrest in MDA-MB-468 cells. Moreover, treatment with DW532 potently and dose-dependently suppressed angiogenesis in vitro and in vivo. Conclusion: DW532 is a dual inhibitor against tubulin and tyrosine kinases, and deserves further development as a novel anti-cancer agent. 相似文献
166.
目的 对合成的新型4-苯胺基喹唑啉类酪氨酸激酶抑制剂TYIG1~TYIG9进行抗肿瘤活性研究,为寻找具有靶向抗肿瘤活性的候选化合物提供依据。方法 采用均相时间分辨荧光(HTRF)法对化合物进行EGFR、VEGFR-2两个靶点的体外活性筛选;采用MTS法对化合物进行肿瘤细胞(A431、A549、H1975、MDA-MB-231)增殖抑制的体外活性评价;采用人肺癌H1975细胞的移植瘤裸鼠模型评价其在动物体内抗肿瘤活性。结果 采用HTRF法从合成的一系列化合物中筛选出化合物TYIG4~TYIG9对EGFR、VEGFR-2激酶的活性较好。MTS法检测得到这6个化合物对4种肿瘤细胞(A431、A549、H1975、MDA-MB-231)均有不同程度的抑制作用,其中TYIG6的增殖抑制作用的选择性更为突出;体内试验结果表明TYIG6能够剂量相关性地抑制肿瘤生长,50、100 mg/kg TYIG6对H1975的相对肿瘤抑制率分别为42.59%、34.92%。结论 TYIG6具有良好的体内外抗肿瘤活性,具有成为新型双靶点酪氨酸激酶抑制剂的潜能,有进一步的研究价值。 相似文献
167.
Kamlesh Sodani Atish Patel Nagaraju Anreddy Satyakam Singh Dong-Hua Yang Rishil J. Kathawala Priyank Kumar Tanaji T. Talele Zhe-Sheng Chen 《Biochemical pharmacology》2014
Multidrug resistance (MDR) is a phenomenon where cancer cells become simultaneously resistant to anticancer drugs with different structures and mechanisms of action. MDR has been shown to be associated with overexpression of ATP-binding cassette (ABC) transporters. Here, we report that telatinib, a small molecule tyrosine kinase inhibitor, enhances the anticancer activity of ABCG2 substrate anticancer drugs by inhibiting ABCG2 efflux transporter activity. Co-incubation of ABCG2-overexpressing drug resistant cell lines with telatinib and ABCG2 substrate anticancer drugs significantly reduced cellular viability, whereas telatinib alone did not significantly affect drug sensitive and drug resistant cell lines. Telatinib at 1 μM did not significantly alter the expression of ABCG2 in ABCG2-overexpressing cell lines. Telatinib at 1 μM significantly enhanced the intracellular accumulation of [3H]-mitoxantrone (MX) in ABCG2-overexpressing cell lines. In addition, telatinib at 1 μM significantly reduced the rate of [3H]-MX efflux from ABCG2-overexpressing cells. Furthermore, telatinib significantly inhibited ABCG2-mediated transport of [3H]-E217βG in ABCG2 overexpressing membrane vesicles. Telatinib stimulated the ATPase activity of ABCG2 in a concentration-dependent manner, indicating that telatinib might be a substrate of ABCG2. Binding interactions of telatinib were found to be in transmembrane region of homology modeled human ABCG2. In addition, telatinib (15 mg/kg) with doxorubicin (1.8 mg/kg) significantly decreased the growth rate and tumor size of ABCG2 overexpressing tumors in a xenograft nude mouse model. These results, provided that they can be translated to humans, suggesting that telatinib, in combination with specific ABCG2 substrate drugs may be useful in treating tumors that overexpress ABCG2. 相似文献
168.
《Expert opinion on biological therapy》2013,13(6):747-758
ABSTRACTIntroduction: In recent years, several clinical trials have evaluated the efficacy and safety of biological therapies in lung cancer. Epidermal growth factor receptor (EGFR) and the axis vascular endothelial growth factor receptor (VEGF/VEGFR) are targeted by small molecules and monoclonal antibodies (mAbs), especially in non-squamous non-small-cell lung cancer (NSCLC).Areas covered: The current state of the art of anti-EGFR and antiangiogenic monoclonal antibodies in metastatic NSCLC is reviewed and discussed.Expert opinion: Bevacizumab and cetuximab are the most studied mAbs in NSCLC, but only bevacizumab is in clinical practice in the first-line setting. Necitumumab is a new anti-EGFR monoclonal antibody that improves survival when combined to cisplatin/gemcitabine chemotherapy and has been approved in first-line advanced NSCLC. Ramucirumab, an antiangiogenic drug binding with high affinity to VEGFR-2, improves the results of chemotherapy alone when administered with docetaxel and has been approved in second-line setting. Moreover, the novel combination of bevacizumab and erlotinib is very promising for the treatment of patients with NSCLC harbouring EGFR mutations. The association of antiangiogenic mAbs and immunotherapy is under investigation too. 相似文献
169.
Ryan Hickey Michael Vouche Daniel Y. Sze Elias Hohlastos Jeremy Collins Todd Schirmang Khairuddin Memon Robert K. Ryu Kent Sato Richard Chen Ramona Gupta Scott Resnick James Carr Howard B. Chrisman Albert A. Nemcek Robert L. Vogelzang Robert J. Lewandowski Riad Salem 《Journal of vascular and interventional radiology : JVIR》2013,24(8):1167-1188
This is the second of a two-part overview of the fundamentals of oncology for interventional radiologists. The first part focused on clinical trials, basic statistics, assessment of response, and overall concepts in oncology. This second part aims to review the methods of tumor characterization; principles of the oncology specialties, including medical, surgical, radiation, and interventional oncology; and current treatment paradigms for the most common cancers encountered in interventional oncology, along with the levels of evidence that guide these treatments. 相似文献
170.