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Ming-Ju Hsieh Cheng Huang Chia-Chieh Lin Chih-Hsin Tang Chih-Yang Lin I-Neng Lee Hsiu-Chen Huang Jui-Chieh Chen 《Molecular carcinogenesis》2020,59(3):293-303
Chondrosarcoma is the second most common form of bone cancer and is characterized by its ability to produce an extracellular matrix of the cartilage. High-grade chondrosarcoma is highly aggressive and can metastasize to other parts of the body. Chondrosarcoma is resistant to both conventional chemotherapy and radiotherapy; hence, the current main treatment is still surgical resection. Doxorubicin (Dox) has been shown to significantly improve patient survival compared with untreated chondrosarcoma. However, for patients with metastasis, surgical resection alone can hardly treat them. In addition, drug resistance is one of the leading causes of death in patients with chondrosarcoma. Secreted proteins can mediate cell-cell interactions in the cancer microenvironment, which may be associated with the development of drug resistance. In the present study, chondrosarcoma cells were treated with Dox, the conditioned medium was then collected and changes in secreted proteins were analyzed using the antibody array. Results showed that the Dox-treated group had the highest secretion of basic fibroblast growth factor (bFGF), indicating the effect of bFGF on Dox sensitivity in chondrosarcoma. Furthermore, lentiviral-mediated knockdown and treatment of exogenous recombinant protein were employed to further investigate the effect of bFGF on Dox resistance. Results demonstrated that bFGF can promote the expression of X-ray repair cross-complementing protein 5 (XRCC5), leading to Dox resistance. Secreted bFGF is likely to be detected in serum, in addition to being a biomarker for predicting Dox resistance, the combination of Dox and bFGF/XRCC5 blockers may be a new therapeutic strategy to improve the efficacy of Dox in future. 相似文献
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Heming Lu Yuying Wu Xu Liu Huixian Huang Hailan Jiang Chaohua Zhu Yuping Man Zhaohong Chen Xianfeng Long Qiang Pang Luxing Peng Xianglong Li Junzhao Gu Shan Deng Ligang Xing 《Oncology research》2020,28(9):929-944
This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis
inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC).
Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone
(CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy.
Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS)
and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2
(VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E
arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus
82.1% and 80.8% versus 63.5% (p=0.091), respectively. The 1- and 2-year distance metastasis-free survival
(DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p=0.031), respectively. Patients with positive
VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative
VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those
in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly
improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival
for patients with positive VEGFR2 expression. 相似文献
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目的:评价2种含磷酸酯单体的底涂剂处理的Y?TZP陶瓷与树脂的粘接及其耐水解性。方法:80枚氧化锆(Y?TZP)瓷片随机分为4组进行不同的表面处理:氧化铝喷喷砂;氧化铝喷砂后以氧化锆底涂剂Z?Prime Plus或Clearfil Ceramic Prime处理;摩擦化学法硅涂层后以硅烷处理。使用树脂水门汀制作粘接试件测试其剪切粘接强度。Y?TZP瓷片表面分别经过2种底涂剂处理后以X射线光电子能谱分析(XPS)检测其表面化学键变化。采用电感耦合等离子体制谱(ICP?MS)测试Y?TZP/树脂粘接界面的磷元素释放量。结果:老化前,与阴性对照组相比,2种含MDP的底涂剂处理均能提高短期粘接强度值,但硅涂层处理组的粘接强度最高。老化后,硅涂层处理组较老化前未有明显变化;喷砂及2种含MDP底涂剂处理组的粘接强度值显著下降(P < 0.05)。XPS在Y?TZP陶瓷使用2种含MDP底涂剂处理后均检测出“?P?O?Zr”键。ICP?MS测试在使用含MDP底涂剂处理的粘接试件的浸泡液中检测到磷元素的释放。结论:水会负面影响磷酸酯单体介导的氧化锆与树脂间的粘接。 相似文献
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Chu-Chih Chen Yin-Han Wang Wei J. Chen Chao A. Hsiung Yue-Liang Leon Guo Shu-Li Julie Wang 《International journal of hygiene and environmental health》2019,222(6):971-980
IntroductionPrenatal exposure to di(2-ethylhexyl) phthalate (DEHP) has been reported to be associated with adverse effects on neurodevelopment that yield behavior syndromes in young children with an estimated median exposure lower than the currently recommended tolerable daily intake (TDI) and reference dose (RfD).ObjectivesOur aim was to derive the benchmark dose for prenatal exposure to DEHP for the neurodevelopmental health in children.MethodsA total of 122 mother-child pairs from the Taiwan Maternal and Infant Cohort Study were analyzed for the dose-response relationship between maternal exposure to DEHP and children's behavioral syndromes evaluated at 8 years (n = 122, 2009), 11 years (n = 96, 2012), and 14 years (n = 78, 2015) of age. We employed a multivariate regression model to assess the statistical associations between the estimated maternal average daily intake of DEHP and child's individual CBCL scores for boys and girls at each separate age, followed by a mixed model for all the children across three ages accounting for individual variations. We then employed structural equation models by combining the children's specific behavioral problem scores at different ages and obtained a simulated overall latent score in relation to maternal exposure. Based on the established dose-response relationship, we derived the benchmark dose (BMD) and the lower limit (BMDL).ResultsAssociations of maternal DEHP exposure (median 4.54) with the Child Behavior Checklist (CBCL) scores were all significant, except for somatic complaints, adjusting for child's age, gender, IQ, and family income. The BMDL, given a benchmark response of 0.10 (0.05) and a background response of 0.05, was 6.01 (2.16) for an integrated CBCL score.ConclusionsThe current TDI (RfD) of 50 (20) for DEHP might not protect pregnant women for their children from behavioral problems. There remains the lack of comparable toxicological data. Further investigations are needed. 相似文献
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