全文获取类型
收费全文 | 829篇 |
免费 | 51篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 50篇 |
妇产科学 | 6篇 |
基础医学 | 96篇 |
口腔科学 | 7篇 |
临床医学 | 52篇 |
内科学 | 184篇 |
皮肤病学 | 1篇 |
神经病学 | 92篇 |
特种医学 | 38篇 |
外科学 | 117篇 |
综合类 | 1篇 |
预防医学 | 27篇 |
眼科学 | 13篇 |
药学 | 63篇 |
肿瘤学 | 131篇 |
出版年
2022年 | 7篇 |
2021年 | 19篇 |
2020年 | 7篇 |
2019年 | 10篇 |
2018年 | 11篇 |
2017年 | 15篇 |
2016年 | 8篇 |
2015年 | 19篇 |
2014年 | 23篇 |
2013年 | 27篇 |
2012年 | 48篇 |
2011年 | 45篇 |
2010年 | 20篇 |
2009年 | 29篇 |
2008年 | 34篇 |
2007年 | 34篇 |
2006年 | 39篇 |
2005年 | 20篇 |
2004年 | 15篇 |
2003年 | 25篇 |
2002年 | 27篇 |
2001年 | 24篇 |
2000年 | 33篇 |
1999年 | 22篇 |
1998年 | 7篇 |
1997年 | 18篇 |
1996年 | 14篇 |
1995年 | 11篇 |
1994年 | 11篇 |
1993年 | 12篇 |
1992年 | 32篇 |
1991年 | 28篇 |
1990年 | 27篇 |
1989年 | 16篇 |
1988年 | 11篇 |
1987年 | 17篇 |
1986年 | 15篇 |
1985年 | 14篇 |
1983年 | 13篇 |
1981年 | 4篇 |
1979年 | 7篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 5篇 |
1975年 | 8篇 |
1973年 | 5篇 |
1971年 | 6篇 |
1969年 | 3篇 |
1967年 | 6篇 |
1965年 | 4篇 |
排序方式: 共有880条查询结果,搜索用时 15 毫秒
21.
Lou X Fan F Messa M Raimondi A Wu Y Looger LL Ferguson SM De Camilli P 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(8):E515-E523
Endocytic recycling of synaptic vesicles after exocytosis is critical for nervous system function. At synapses of cultured neurons that lack the two "neuronal" dynamins, dynamin 1 and 3, smaller excitatory postsynaptic currents are observed due to an impairment of the fission reaction of endocytosis that results in an accumulation of arrested clathrin-coated pits and a greatly reduced synaptic vesicle number. Surprisingly, despite a smaller readily releasable vesicle pool and fewer docked vesicles, a strong facilitation, which correlated with lower vesicle release probability, was observed upon action potential stimulation at such synapses. Furthermore, although network activity in mutant cultures was lower, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity was unexpectedly increased, consistent with the previous report of an enhanced state of synapsin 1 phosphorylation at CaMKII-dependent sites in such neurons. These changes were partially reversed by overnight silencing of synaptic activity with tetrodotoxin, a treatment that allows progression of arrested endocytic pits to synaptic vesicles. Facilitation was also counteracted by CaMKII inhibition. These findings reveal a mechanism aimed at preventing synaptic transmission failure due to vesicle depletion when recycling vesicle traffic is backed up by a defect in dynamin-dependent endocytosis and provide new insight into the coupling between endocytosis and exocytosis. 相似文献
22.
Pichini S Marchei E Vagnarelli F Tarani L Raimondi F Maffucci R Sacher B Bisceglia M Rapisardi G Elicio MR Biban P Zuccaro P Pacifici R Pierantozzi A Morini L 《Alcoholism, clinical and experimental research》2012,36(3):417-424
Background: This study estimated in 7 Italian cities the prevalence of prenatal exposure to ethanol by determining fatty acid ethyl esters (FAEEs; palmitic, palmitoleic, stearic, oleic, linoleic, linolenic, and arachidonic esters) and ethyl glucuronide (EtG) in neonatal meconium samples. Methods: A total of 607 meconium samples were obtained from neonatal wards of 7 public hospitals: Verona and San Daniele del Friuli in the northeast of the country, Reggio Emilia in the middle east, Florence and Rome in the center, and Naples and Crotone in the southwest of the peninsula. Meconium biomarkers were assessed by a validated methodology using liquid chromatography–tandem mass spectrometry and the results categorized using the accepted cutoff of 2 nmol/g total amount of 7 FAEEs and 2 nmol/g EtG, to differentiate between heavy maternal ethanol use during pregnancy and occasional or no use at all. Results: On the basis of the above‐reported cutoffs, the overall prevalence of newborns prenatally exposed to maternal ethanol was 7.9%: 0% in Verona, 4.0% in San Daniele del Friuli, 4.9% in Naples, 5.0% in Florence, 6.2% in Crotone, up to 10.6% in Reggio Emilia, and 29.4% in Rome. Low maternal education level and younger maternal age were associated with biomarker scores over the cutoff. There was also a significant correlation between the highest percentage of prenatal exposure in the capital and certain maternal sociodemographic characteristics. Conclusions: These results indicate considerable variability in the prevalence of fetal exposure to ethanol in different Italian cities, as determined by the objective measurement of biomarkers in meconium. These data, together with previous ones obtained in Barcelona, Spain, indicate that gestational ethanol exposure is widespread, at least in parts of Europe. 相似文献
23.
Loken MR Alonzo TA Pardo L Gerbing RB Raimondi SC Hirsch BA Ho PA Franklin J Cooper TM Gamis AS Meshinchi S 《Blood》2012,120(8):1581-1588
Early response to induction chemotherapy is a predictor of outcome in acute myeloid leukemia (AML). We determined the prevalence and significance of postinduction residual disease (RD) by multidimensional flow cytometry (MDF) in children treated on Children's Oncology Group AML protocol AAML03P1. Postinduction marrow specimens at the end of induction (EOI) 1 or 2 or at the end of therapy from 249 patients were prospectively evaluated by MDF for RD, and presence of RD was correlated with disease characteristics and clinical outcome. Of the 188 patients in morphologic complete remission at EOI1, 46 (24%) had MDF-detectable disease. Those with and without RD at the EOI1 had a 3-year relapse risk of 60% and 29%, respectively (P < .001); the corresponding relapse-free survival was 30% and 65% (P < .001). Presence of RD at the EOI2 and end of therapy was similarly predictive of poor outcome. RD was detected in 28% of standard-risk patients in complete remission and was highly associated with poor relapse-free survival (P = .008). In a multivariate analysis, including cytogenetic and molecular risk factors, RD was an independent predictor of relapse (P < .001). MDF identifies patients at risk of relapse and poor outcome and can be incorporated into clinical trials for risk-based therapy allocation. This study was registered at www.clinicaltrials.gov as NCT00070174. 相似文献
24.
Foderaro Giuseppe Isella Valeria Mazzone Andrea Biglia Elena Di Gangi Marco Pasotti Fabrizio Sansotera Flavia Grobberio Monica Raimondi Vanessa Mapelli Cristina Ferri Francesca Impagnatiello Valentina Ferrarese Carlo Appollonio Ildebrando Marco 《Neurological sciences》2022,43(5):3053-3063
Neurological Sciences - Mini-Mental State Examination (MMSE) is one of the most used tests for the screening of global cognition in patients with neurological and medical disorders. Norms for the... 相似文献
25.
Matteo Donadon Andrea Forastieri Molinari Francesco Corazzi Laura Rocchi Paola Zito Matteo Cimino Guido Costa Ferdinando Raimondi Guido Torzilli 《World journal of surgery》2016,40(9):2202-2212
Background
The Pringle maneuver, which is performed during liver surgery to reduce blood loss, may result in liver ischemia/reperfusion injury resulting in metabolic, immunological, and microvascular changes, which may lead to hepatocellular damage. The aim of this study was the investigation of the effects of N-acetylcysteine (NAC) and methylprednisolone (MET) in the modulation of liver warm ischemia during hepatic resection.Methods
Forty-eight patients were enrolled in a pilot double-blind, randomized clinical trial. The patients received either NAC, MET, or placebo. The primary endpoint was the reduction in postoperative alanine aminotransferase and bilirubin. The secondary endpoint was the difference in morbidity and mortality.Results
All the 48 patients had liver resection with no mortality. Morbidity was observed in 8 (16 %) patients equally distributed among the groups. There was a significant favorable recovery of liver function tests in patients treated with NAC or MET compared with the placebo when the Pringle maneuver exceeded 70 min.Conclusions
The administration of NAC or MET prior to the Pringle maneuver during hepatic resection is associated with lower postoperative aberration in liver function tests compared with placebo when the Pringle maneuver exceeded 70 min. Larger studies are required to validate our findings and to investigate the specific role of NAC and MET in liver surgery.26.
27.
Nonclinical pharmacokinetics and metabolism of EPZ‐5676, a novel DOT1L histone methyltransferase inhibitor
下载免费PDF全文
![点击此处可从《Biopharmaceutics & drug disposition》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Aravind Basavapathruni Edward J. Olhava Scott R. Daigle Carly A. Therkelsen Lei Jin P. Ann Boriack‐Sjodin Christina J. Allain Christine R. Klaus Alejandra Raimondi Margaret Porter Scott Angelos Dovletoglou Victoria M. Richon Roy M. Pollock Robert A. Copeland Mikel P. Moyer Richard Chesworth Paul G. Pearson Nigel J. Waters 《Biopharmaceutics & drug disposition》2014,35(4):237-252
(2R,3R,4S,5R)‐2‐(6‐Amino‐9H‐purin‐9‐yl)‐5‐((((1r,3S)‐3‐(2‐(5‐(tert‐butyl)‐1H‐benzo[d]imidazol‐2‐yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran‐3,4‐diol (EPZ‐5676) is a novel DOT1L histone methyltransferase inhibitor currently in clinical development for the treatment of MLL‐rearranged leukemias. This report describes the preclinical pharmacokinetics and metabolism of EPZ‐5676, an aminonucleoside analog with exquisite target potency and selectivity that has shown robust and durable tumor growth inhibition in preclinical models. The in vivo pharmacokinetics in mouse, rat and dog were characterized following i.v. and p.o. administration; EPZ‐5676 had moderate to high clearance, low oral bioavailability with a steady‐state volume of distribution 2–3 fold higher than total body water. EPZ‐5676 showed biexponential kinetics following i.v. administration, giving rise to a terminal elimination half‐life (t1/2) of 1.1, 3.7 and 13.6 h in mouse, rat and dog, respectively. The corresponding in vitro ADME parameters were also studied and utilized for in vitro–in vivo extrapolation purposes. There was good agreement between the microsomal clearance and the in vivo clearance implicating hepatic oxidative metabolism as the predominant elimination route in preclinical species. Furthermore, low renal clearance was observed in mouse, approximating to fu‐corrected glomerular filtration rate (GFR) and thus passive glomerular filtration. The metabolic pathways across species were studied in liver microsomes in which EPZ‐5676 was metabolized to three monohydroxylated metabolites (M1, M3 and M5), one N‐dealkylated product (M4) as well as an N‐oxide (M6). Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
28.
John E. Campbell Kevin W. Kuntz Sarah K. Knutson Natalie M. Warholic Heike Keilhack Tim J. Wigle Alejandra Raimondi Christine R. Klaus Nathalie Rioux Akira Yokoi Satoshi Kawano Yukinori Minoshima Hyeong-Wook Choi Margaret PorterScott Nigel J. Waters Jesse J. Smith Richard Chesworth Mikel P. Moyer RobertA. Copeland 《ACS medicinal chemistry letters》2015,6(5):491-495
29.