全文获取类型
收费全文 | 10261篇 |
免费 | 656篇 |
国内免费 | 43篇 |
专业分类
耳鼻咽喉 | 185篇 |
儿科学 | 328篇 |
妇产科学 | 254篇 |
基础医学 | 1310篇 |
口腔科学 | 431篇 |
临床医学 | 698篇 |
内科学 | 2436篇 |
皮肤病学 | 198篇 |
神经病学 | 855篇 |
特种医学 | 304篇 |
外科学 | 1650篇 |
综合类 | 48篇 |
预防医学 | 843篇 |
眼科学 | 113篇 |
药学 | 545篇 |
中国医学 | 45篇 |
肿瘤学 | 717篇 |
出版年
2023年 | 77篇 |
2022年 | 150篇 |
2021年 | 338篇 |
2020年 | 185篇 |
2019年 | 291篇 |
2018年 | 357篇 |
2017年 | 273篇 |
2016年 | 246篇 |
2015年 | 294篇 |
2014年 | 369篇 |
2013年 | 503篇 |
2012年 | 684篇 |
2011年 | 706篇 |
2010年 | 468篇 |
2009年 | 389篇 |
2008年 | 605篇 |
2007年 | 565篇 |
2006年 | 545篇 |
2005年 | 558篇 |
2004年 | 514篇 |
2003年 | 445篇 |
2002年 | 384篇 |
2001年 | 207篇 |
2000年 | 223篇 |
1999年 | 207篇 |
1998年 | 95篇 |
1997年 | 67篇 |
1996年 | 59篇 |
1995年 | 54篇 |
1994年 | 55篇 |
1993年 | 49篇 |
1992年 | 103篇 |
1991年 | 68篇 |
1990年 | 79篇 |
1989年 | 82篇 |
1988年 | 63篇 |
1987年 | 70篇 |
1986年 | 55篇 |
1985年 | 47篇 |
1984年 | 40篇 |
1983年 | 32篇 |
1982年 | 20篇 |
1980年 | 22篇 |
1979年 | 26篇 |
1976年 | 22篇 |
1975年 | 22篇 |
1974年 | 26篇 |
1973年 | 26篇 |
1971年 | 22篇 |
1970年 | 19篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
1.
Chouraqui Jean-Pierre Tavoularis Gabriel Simeoni Umberto Ferry Constance Turck Dominique 《European journal of nutrition》2020,59(1):67-80
European Journal of Nutrition - The French Nutri-Bébé 2013 study aimed to assess the nutritional intake of infants and young children in comparison with the recommendations of the 2013... 相似文献
2.
3.
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
4.
Enrique Luengo Izaskun Buendia Cristina Fernndez‐Mendívil Paula Trigo‐Alonso Pilar Negredo Patrycja Michalska Borja Hernndez‐García Cristina Snchez‐Ramos Juan A. Bernal Tsuneya Ikezu Rafael Len Manuela G. Lpez 《Journal of pineal research》2019,67(1)
Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTauP301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTauP301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD. 相似文献
5.
6.
7.
Marco Maruzzo Umberto Basso Eugenio Borsatti Laura Evangelista Filippo Alongi Orazio Caffo Francesca Maines Sara Galuppo Rocco De Vivo Fable Zustovich Dario Palleschi Andrea Zivi Teodoro Sava Mariella Sorarù Roberto Iacovelli Maurizio Nicodemo Susanne Baier Lucia Fratino Vittorina Zagonel 《Clinical genitourinary cancer》2019,17(1):e187-e194
Background
Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.Patients and Methods
We conducted a multicenter retrospective analysis in the Triveneto region of Italy.Results
One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P < .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P < .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia.Conclusion
This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined. 相似文献8.
9.
10.
M. L. Hernández J. J. Fernández-Ruiz R. de Miguel J. A. Ramos 《Journal of neural transmission (Vienna, Austria : 1996)》1991,83(1-2):77-84
Summary In this work, we have studied the time-course of the effects of pharmacological administration of ovarian steroids on tyrosine hydroxylase (TH) activity in the limbic forebrain of ovariectomized rats. Administration of estradiol produced a late decrease in TH activity. This effect was found 24 hours after the last steroid injection, disappearing at 32 hours. It was antagonized by progesterone, since a single injection of this steroid to estradiol-pretreated rats reversed to control values the estradiol-induced decrease. Nevertheless, the administration of progesterone after estradiol treatment caused a short-time decrease in the limbic activity of TH, which was observed 4 hours after the last steroid injection, disappearing subsequently. On the other hand, the administration of progesterone alone produced a biphasic effect, with a reduction at 24 hours, followed by an increase at 32 hours. These effects were only observed in the animals non-treated with estradiol, disappearing with a previous treatment with estrogens. Hence, it can be concluded that both ovarian steroids may affect the limbic TH activity. Thus, estradiol produced a late inhibitory effect on the activity of this enzyme, which was antagonized by progesterone. Administration of the last one to estradiol-treated rats produced a short-time inhibitory effect, whereas its administration to non-treated rats produced a late biphasic effect (inhibition followed by stimulation), which was not observed in estradiol-treated rats. 相似文献