全文获取类型
收费全文 | 16448篇 |
免费 | 962篇 |
国内免费 | 147篇 |
专业分类
耳鼻咽喉 | 145篇 |
儿科学 | 311篇 |
妇产科学 | 476篇 |
基础医学 | 1888篇 |
口腔科学 | 542篇 |
临床医学 | 1421篇 |
内科学 | 4342篇 |
皮肤病学 | 424篇 |
神经病学 | 1360篇 |
特种医学 | 354篇 |
外科学 | 2355篇 |
综合类 | 501篇 |
一般理论 | 2篇 |
预防医学 | 1236篇 |
眼科学 | 236篇 |
药学 | 961篇 |
5篇 | |
中国医学 | 234篇 |
肿瘤学 | 764篇 |
出版年
2024年 | 13篇 |
2023年 | 155篇 |
2022年 | 349篇 |
2021年 | 697篇 |
2020年 | 382篇 |
2019年 | 535篇 |
2018年 | 703篇 |
2017年 | 442篇 |
2016年 | 430篇 |
2015年 | 511篇 |
2014年 | 782篇 |
2013年 | 937篇 |
2012年 | 1411篇 |
2011年 | 1417篇 |
2010年 | 793篇 |
2009年 | 733篇 |
2008年 | 1107篇 |
2007年 | 1049篇 |
2006年 | 1013篇 |
2005年 | 915篇 |
2004年 | 804篇 |
2003年 | 652篇 |
2002年 | 631篇 |
2001年 | 97篇 |
2000年 | 92篇 |
1999年 | 86篇 |
1998年 | 104篇 |
1997年 | 71篇 |
1996年 | 78篇 |
1995年 | 69篇 |
1994年 | 50篇 |
1993年 | 35篇 |
1992年 | 38篇 |
1991年 | 29篇 |
1990年 | 25篇 |
1989年 | 21篇 |
1988年 | 18篇 |
1987年 | 15篇 |
1986年 | 24篇 |
1985年 | 19篇 |
1984年 | 22篇 |
1983年 | 17篇 |
1982年 | 24篇 |
1981年 | 20篇 |
1980年 | 22篇 |
1978年 | 12篇 |
1974年 | 11篇 |
1973年 | 19篇 |
1972年 | 10篇 |
1971年 | 8篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
1.
2.
N. S. Hari Narayana Moorthy Sergio F. Sousa Maria J. Ramos Pedro A. Fernandes 《Medicinal chemistry research》2016,25(7):1340-1357
Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets. 相似文献
3.
4.
Maria Gonzalez-Cao Cristina Carrera Juan Francisco Rodriguez Moreno Pedro Rodríguez-Jiménez Mónica Antoñanzas Basa Rosa Feltes Ochoa Teresa Puertolas Eva Muñoz-Couselo José Luis Manzano Ivan Marquez-Rodas Juan Martín-Liberal Ainara Soria Pilar Lopez Criado Almudena Garcia-Castaño Aram Boada Pablo Ayala de Miguel Susana Puig Guillermo Crespo Alfonso Berrocal 《Journal of the American Academy of Dermatology》2021,84(5):1412-1415
5.
6.
Pedro Lopez Matheus Daros Pinto Ronei Silveira Pinto 《Ultrasound in medicine & biology》2019,45(2):612-616
In the work described here, our aim was to determine, in an elderly population, changes in muscle thickness (MT), cross-sectional area (CSA) and echo intensity (EI) of the quadriceps muscles at four time points (0, 5, 10 and 15 min; i.e., T0, T5, T10 and T15, respectively) after changing from a standing to supine position. Twenty-one elderly participants (14 men: 68.1 ± 4.6 y; 8 women: 66.8 ± 4.1 y) were evaluated at four time points. Rectus femoris CSA (RFCSA), MT and EI of the quadriceps femoris (QF) muscles were assessed. EI significantly increased from T0 to T5, T10 and T15 (p < 0.001), whereas no differences were observed between T5 and T15 in the rectus femoris (RFEI), vastus intermedius (VIEI) and quadriceps femoris (QFEI). No differences were observed between any time points in the RFCSA and MT of QF muscles. In summary, these results suggest that periods >5 min are not necessary to obtain consistent MT and EI measurements of quadriceps femoris muscles in the elderly population. 相似文献
7.
8.
9.
目的:观察灯盏乙素(Scu)对β淀粉样蛋白(Aβ)诱导的细胞模型中1,4,5-三磷酸肌醇受体(IP3R)-Ca2+途径的影响,探讨其在阿尔茨海默病(AD)病程中可能发挥的积极作用。方法:选用神经母细胞瘤细胞分为对照组、Scu处理组、Aβ处理组、Aβ+Scu (高、中、低)处理组及Aβ+IP3R拮抗剂组,用CCK-8法筛选药物浓度并检测各组细胞生存率;用酶联免疫吸附法检测各组细胞中1,4,5-三磷酸肌醇(IP3)的含量;用蛋白印迹和实时荧光定量聚合酶链反应方法检测各组细胞IP3R和凋亡相关因子Caspase-3、Bcl-2、Bax的蛋白及mRNA的表达水平;用激光共聚焦显微镜观察各组细胞内Ca2+浓度的变化;用AnnexinV/PI双染法测定各组细胞的凋亡率。结果:与对照组和Scu处理组相比,Aβ处理组细胞存活率下降,IP3含量升高,IP3R、Bax和Caspase-3的蛋白及mRNA表达上调,Bcl-2蛋白及mRNA的表达下调,细胞胞浆内Ca2+浓度及细胞凋亡率升高;Aβ+Scu处理组细胞中各检测指标的变化与Aβ处理组的结果正好相反,IP3R通道下游指标的变化与Aβ+IP3R拮抗剂组基本一致。结论:Scu能够下调通路蛋白IP3、IP3R的表达,抑制Aβ介导的Ca2+内流所致的细胞凋亡,可能通过对IP3R-Ca2+途径的调控来影响AD病程。 相似文献
10.
Maria C. Chammas Andre C. Oliveira Mario J. D´Ávilla Pedro H. Moraes Marcelo Straus Takahashi 《Ultrasound in medicine & biology》2019,45(1):50-55
We prospectively evaluated the effectiveness of contrast-enhanced ultrasonography (CEUS) for differentiation of benign versus malignant portal vein thrombosis (PVT). We studied a total of 43 patients with chronic liver disease, hepatocellular carcinoma-suggestive nodules and confirmed PVT, in whom the nature of the PVT was confirmed by follow-up imaging (US, computed tomography and/or magnetic resonance imaging) performed up to 6 mo after CEUS. PVT was assessed by US, Doppler US and CEUS with respect to vessel wall disruption and/or invasion, color Doppler vascularization, pulsed Doppler vascularization pattern and CEUS enhancement and vascularization pattern, and thrombi were classified as benign or malignant based on these findings. Follow-up studies revealed malignant PVT in 22 of the 43 patients (51%) and benign PVT in 21 patients (49%). CEUS findings were consistent with follow-up studies in 41 of the 43 patients (95%), with κ?=?0.903 (p < 0.0001), sensitivity?=?91% and specificity?=?100%, indicating that CEUS can be confidently used to differentiate benign from malignant portal vein thrombosis in the setting of chronic liver disease. 相似文献