全文获取类型
收费全文 | 5800篇 |
免费 | 373篇 |
国内免费 | 365篇 |
出版年
2024年 | 14篇 |
2023年 | 83篇 |
2022年 | 170篇 |
2021年 | 307篇 |
2020年 | 170篇 |
2019年 | 215篇 |
2018年 | 237篇 |
2017年 | 175篇 |
2016年 | 228篇 |
2015年 | 359篇 |
2014年 | 395篇 |
2013年 | 502篇 |
2012年 | 555篇 |
2011年 | 431篇 |
2010年 | 279篇 |
2009年 | 246篇 |
2008年 | 255篇 |
2007年 | 250篇 |
2006年 | 237篇 |
2005年 | 218篇 |
2004年 | 142篇 |
2003年 | 117篇 |
2002年 | 117篇 |
2001年 | 118篇 |
2000年 | 90篇 |
1999年 | 119篇 |
1998年 | 51篇 |
1997年 | 63篇 |
1996年 | 55篇 |
1995年 | 30篇 |
1994年 | 36篇 |
1993年 | 32篇 |
1992年 | 41篇 |
1991年 | 35篇 |
1990年 | 29篇 |
1989年 | 24篇 |
1988年 | 19篇 |
1987年 | 13篇 |
1986年 | 18篇 |
1985年 | 13篇 |
1984年 | 8篇 |
1983年 | 7篇 |
1982年 | 6篇 |
1981年 | 11篇 |
1980年 | 4篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1972年 | 2篇 |
1969年 | 2篇 |
1966年 | 1篇 |
排序方式: 共有6538条查询结果,搜索用时 15 毫秒
891.
892.
893.
894.
Jinxing Hu Yufei Han Jingtao Wang Yue Liu Yanfang Zhao Yajing Liu Ping Gong 《Bioorganic & medicinal chemistry》2018,26(8):1810-1822
Based upon the modeling binding mode of marketed AZD9291 with T790M, a series of N-9-Diphenyl-9H-purin-2-amine derivatives were designed and synthesized with the purpose to overcome the drug resistance resulted from T790M/L858R double mutations. The most potent compound 23a showed excellent enzyme inhibitory activities and selectivity with nanomolar IC50 values for both the single T790M and double T790M/L858R mutant EGFRs, and was more than 8-fold selective for wild type EGFR. Compound 23a displayed strong antiproliferative activity against the H1975 non-small cell lung cancer (NSCLC) cells bearing T790M/L858R. And it was less potent against A549 (WT EGFR and k-Ras mutation) and HT-29 (non-special gene type) cells, showing a high safety index. 相似文献
895.
Paul M. O Neill Paul A. Stocks Sunil Sabbani Natalie L. Roberts Richard K. Amewu Emma R. Shore Ghaith Aljayyoussi I?igo Angulo-Barturén María Belén Santiago Ferrer Bazaga María Santos Martínez Brice Campo Raman Sharma Susan A. Charman Eileen Ryan Gong Chen David M. Shackleford Stephen A. Ward 《Bioorganic & medicinal chemistry》2018,26(11):2996-3005
A series of aryl carboxamide and benzylamino dispiro 1,2,4,5-tetraoxane analogues have been designed and synthesized in a short synthetic sequence from readily available starting materials. From this series of endoperoxides, molecules with in vitro IC50s versus Plasmodium falciparum (3D7) as low as 0.84?nM were identified. Based on an assessment of blood stability and in vitro microsomal stability, N205 (10a) was selected for rodent pharmacokinetic and in vivo antimalarial efficacy studies in the mouse Plasmodium berghei and Plasmodium falciparum Pf3D70087/N9 severe combined immunodeficiency (SCID) mouse models. The results indicate that the 4-benzylamino derivatives have excellent profiles with a representative of this series, N205, an excellent starting point for further lead optimization studies. 相似文献
896.
Junfang Li Changhong Lu Wugang Wang Kun Gong Liang Zhao Zhibin Wang 《Cardiovascular ultrasound》2018,16(1):32
Background and Objectives
This study aimed to assess the changes of RA function in patients with obstructive sleep apnea syndrome (OSAS) using velocity vector imaging (VVI) and to evaluate the application of VVI technology.Methods
According to the apnea–hypopnea index (AHI), 71 patients with OSAS were divided into three groups: mild, moderate, and severe. A total of 30 cases of healthy subjects were enrolled as the control group. Digital images of apex four-chamber views were acquired to measure the right atrium (RA) linear dimensions and volume parameters including RA longitudinal diameter (RAL), transverse diameter (RAT), RA maximum volume (Vmax), RA minimum volume (Vmin), right atrial volume before contraction (Vpre). Right atrial volume parameters were corrected by body surface area (VImax, VImin, VIpre). The total right atrial emptying fraction (RATEF), right atrial passive emptying fraction (RAPEF), right atrial active contraction emptying fraction (RAAEF) were calculated. The VVI data measuring right atrial global strain (RA-GLS), right atrial strain rate in ventricular systolic phase (RA-SRs), right atrial strain rate in ventricular early diastolic phase (RA-SRe), right atrial strain rate in ventricular late diastolic phase (RA-SRa).Results
- 1.RA linear dimensions and volume parameters in severe OSAS were higher than those of control group. RAPEF in severe group was lower than control group and mild OSAS group (t?= 2.681, P?=?0.021; t?= 2.985, P?=?0.011; respectively). RAAEF in OSAS moderate group was higher than that of control group (t?= 3.006, P?=?0.02), and without statistical difference (P?>?0.05) in the severe OSAS group and the control group.
- 2.RA-GLS in moderate OSAS group was significantly lower than that of control group (t?= 2.333, P?=?0.040) and reduced more obvious in the severe OSAS group (vs control, t?= 3.25, P?=?0.008, vs mild; t?= 3.011, P?=?0.012; respectively). RA-SRe in moderate and severe OSAS groups were lower than control group (t?= 2.466, P?=?0.031; t?= 3.547, P?=?0.005; respectively). RA-SRs of OSAS in severe group was lower than that of control and mild groups (t?= 3.665, P?=?0.004; t?= 3.204, P?=?0.008; respectively). RA-SRa in severe OSAS group was lower than that of control group (t?= 2.425, P?=?0.034).
- 3.Multivariate regression analysis showed that RA-GLS and RA-SRe were independently correlated with AHI (t?=???2.738, P?=?0.010; t?=???2.191, P?=?0.036; respectively).
Conclusion
RA function was impaired in patients with OSAS. On hemodynamics, the change of RA function performed increased of reserve function, reduced pipeline function and increased of contraction function. However, the strain and strain rate reduced in different degree. RA-GLS and RA-SRe decreased the earliest, which suggested that strain and strain rate were the parameters which can reflect myocardial function damage earliest. VVI can more earlier and accurately detect myocardial dysfunction of right atrium in patients with OSAS, which is expected to be a worthy technique for early clinical therapy in patients with OSAS.897.
898.
Supplementary choline attenuates olive oil lipid emulsion‐induced enterocyte apoptosis through suppression of CELF1/AIF pathway
下载免费PDF全文
![点击此处可从《Journal of cellular and molecular medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Jun‐Kai Yan Jie Zhu Zi‐Zhen Gong Jie Wen Yong‐Tao Xiao Tian Zhang Wei Cai 《Journal of cellular and molecular medicine》2018,22(3):1562-1573
Enterocyte apoptosis induced by lipid emulsions is a key cause of intestinal atrophy under total parenteral nutrition (TPN) support, and our previous work demonstrated that olive oil lipid emulsion (OOLE) could induce enterocyte apoptosis via CUGBP, Elav‐like family member 1 (CELF1)/ apoptosis‐inducing factor (AIF) pathway. As TPN‐associated complications are partially related to choline deficiency, we aimed to address whether choline supplementation could attenuate OOLE‐induced enterocyte apoptosis. Herein we present evidence that supplementary choline exhibits protective effect against OOLE‐induced enterocyte apoptosis both in vivo and in vitro. In a rat model of TPN, substantial reduction in apoptotic rate along with decreased expression of CELF1 was observed when supplementary choline was added to OOLE. In cultured Caco‐2 cells, supplementary choline attenuated OOLE‐induced apoptosis and mitochondria dysfunction by suppressing CELF1/AIF pathway. Compared to OOLE alone, the expression of CELF1 and AIF was significantly decreased by supplementary choline, whereas the expression of Bcl‐2 was evidently increased. No obvious alterations were observed in Bax expression and caspase‐3 activation. Mechanistically, supplementary choline repressed the expression of CELF1 by increasing the recruitment of CELF1 mRNA to processing bodies, thus resulting in suppression of its protein translation. Taken together, our data suggest that supplementary choline exhibits effective protection against OOLE‐induced enterocyte apoptosis, and thus, it has the potential to be used for the prevention and treatment of TPN‐induced intestinal atrophy. 相似文献
899.
FGF1 improves functional recovery through inducing PRDX1 to regulate autophagy and anti‐ROS after spinal cord injury
下载免费PDF全文
![点击此处可从《Journal of cellular and molecular medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Jiawei Li Qingqing Wang Hanxiao Cai Zili He Haoli Wang Jian Chen Zengming Zheng Jiayu Yin Zhiyong Liao Huazi Xu Jian Xiao Fanghua Gong 《Journal of cellular and molecular medicine》2018,22(5):2727-2738
Fibroblast growth factor 1 (FGF1) is thought to exert protective and regenerative effects on neurons following spinal cord injury (SCI), although the mechanism of these effects is not well understood. The use of FGF1 as a therapeutic agent is limited by its lack of physicochemical stability and its limited capacity to cross the blood‐spinal cord barrier. Here, we demonstrated that overexpression of FGF1 in spinal cord following SCI significantly reduced tissue loss, protected neurons in the ventricornu, ameliorated pathological morphology of the lesion, dramatically improved tissue recovery via neuroprotection, and promoted axonal regeneration and remyelination both in vivo and in vivo. In addition, the autophagy and the expression levels of PRDX1 (an antioxidant protein) were induced by AAV‐FGF1 in PC12 cells after H2O2 treatment. Furthermore, the autophagy levels were not changed in PRDX1‐suppressing cells that were treated by AAV‐FGF1. Taken together, these results suggest that FGF1 improves functional recovery mainly through inducing PRDX1 expression to increase autophagy and anti‐ROS activity after SCI. 相似文献
900.