全文获取类型
收费全文 | 1336篇 |
免费 | 118篇 |
国内免费 | 4篇 |
专业分类
耳鼻咽喉 | 10篇 |
儿科学 | 11篇 |
妇产科学 | 13篇 |
基础医学 | 211篇 |
口腔科学 | 14篇 |
临床医学 | 133篇 |
内科学 | 401篇 |
皮肤病学 | 20篇 |
神经病学 | 154篇 |
特种医学 | 18篇 |
外科学 | 231篇 |
综合类 | 3篇 |
现状与发展 | 1篇 |
预防医学 | 63篇 |
眼科学 | 7篇 |
药学 | 122篇 |
中国医学 | 2篇 |
肿瘤学 | 44篇 |
出版年
2023年 | 9篇 |
2022年 | 41篇 |
2021年 | 47篇 |
2020年 | 27篇 |
2019年 | 41篇 |
2018年 | 44篇 |
2017年 | 28篇 |
2016年 | 28篇 |
2015年 | 39篇 |
2014年 | 37篇 |
2013年 | 77篇 |
2012年 | 92篇 |
2011年 | 110篇 |
2010年 | 63篇 |
2009年 | 62篇 |
2008年 | 81篇 |
2007年 | 81篇 |
2006年 | 94篇 |
2005年 | 94篇 |
2004年 | 103篇 |
2003年 | 69篇 |
2002年 | 69篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 8篇 |
1998年 | 17篇 |
1997年 | 15篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1962年 | 2篇 |
1957年 | 2篇 |
1956年 | 4篇 |
1954年 | 3篇 |
1944年 | 1篇 |
1941年 | 1篇 |
1940年 | 1篇 |
1928年 | 1篇 |
1914年 | 1篇 |
1912年 | 1篇 |
1875年 | 2篇 |
排序方式: 共有1458条查询结果,搜索用时 15 毫秒
41.
The Pharmacokinetics and Pharmacodynamics of Pulmonary Mycobacterium avium Complex Disease Treatment
van Ingen J Egelund EF Levin A Totten SE Boeree MJ Mouton JW Aarnoutse RE Heifets LB Peloquin CA Daley CL 《American journal of respiratory and critical care medicine》2012,186(6):559-565
Rationale: Currently recommended multidrug treatment regimens for Mycobacterium avium complex (MAC) lung disease yield limited cure rates. This results, in part, from incomplete understanding of the pharmacokinetics and pharmacodynamics of the drugs. Objectives: To study pharmacokinetics, pharmacodynamics, and drug interactions of multidrug treatment regimens in a large cohort of patients with MAC lung disease. Methods: We retrospectively collected pharmacokinetic data of all patients treated for MAC lung disease in the Adult Care Unit at National Jewish Health, Denver, Colorado, in the January 2006 to January 2010 period; we retrospectively calculated areas under the time-concentration curve (AUC). Minimum inhibitory concentrations (MIC) of their MAC isolates were retrieved for pharmacodynamic calculations. Measurements and Main Results: We included 531 pharmacokinetic analyses, performed for 481 patients (84% females; mean age, 63 yr; mean body mass index, 21.6). Peak serum concentrations (C(max)) below target range were frequent for ethambutol (48% of patients); clarithromycin (56%); and azithromycin (35%). Concurrent administration of rifampicin led to 68%, 23%, and 10% decreases in C(max) of clarithromycin, azithromycin, and moxifloxacin. C(max)/MIC or AUC/MIC ratios associated with bactericidal activity were seldom met; 57% of patients achieved target ratios for ethambutol, versus 42% for clarithromycin, 19% for amikacin, 18% for rifampicin, and 11% for moxifloxacin. Conclusions: Currently recommended regimens for MAC lung disease yield important pharmacologic interactions and low concentrations of key drugs including macrolides. Pharmacodynamic indices for rifampicin, clarithromycin, amikacin, and moxifloxacin are seldom met. This may partly explain the poor outcomes of currently recommended treatment regimens. Trials of new drugs and new dosing strategies are needed. 相似文献
42.
43.
Zamir Shorer Ruth Shaco-Levy Vered Pinsk Leonid Kachko Jacov Levy 《Pediatric neurology》2013,48(4):311-313
Congenital insensitivity to pain with anhidrosis is a rare disease affecting the nervous system. The patients present with unexplained fever from poor thermoregulation and inability to sweat. Because of the indifference to pain, they manifest frequent traumatic and infectious injuries. Evaluations of these patients include investigation of the hypotonia and weakness evident in this group of patients. We report four patients presenting characteristic features of congenital insensitivity to pain with anhidrosis who carry an identical mutation in the TRK-A gene and who underwent nerve and skeletal muscle biopsies. All four patients had normal sensory and motor conduction studies but lacked sympathetic skin responses. Examination of the skeletal muscles biopsies obtained from two of the patients disclosed marked myopathic changes. The muscle biopsy of a third patient showed mild variation in muscle fibers and the fourth patient's muscle biopsy showed type 1 fiber predominance. Electron microscopy studies revealed remarkable decrease in the number of small caliber-myelinated and unmyelinated nerve fibers. We assume that the variable histological findings in the muscle biopsies of these patients reflect a variation in congenital insensitivity to pain with anhidrosis patients that is not related to their genetic mutation. 相似文献
44.
Jong Bong Lee Simon Zhou Manting Chiang Xiaowei Zang Tae Hwan Kim Leonid Kagan 《Biopharmaceutics & drug disposition》2020,41(4-5):192-205
The aim of the study was to develop a physiologically-based pharmacokinetic (PBPK) model to describe and predict whole-body disposition of doxorubicin following intravenous administration. The PBPK model was established using previously published data in mice and included 10 tissue compartments: lungs, heart, brain, muscle, kidneys, pancreas, intestine, liver, spleen, adipose tissue, and plasma. Individual tissues were described by either perfusion-limited or permeability-limited models. All parameters were simultaneously estimated and the final model was able to describe murine data with good precision. The model was used for predicting doxorubicin disposition in rats, rabbits, dogs, and humans using interspecies scaling approaches and was qualified using plasma and tissue observed data. Reasonable prediction of the plasma pharmacokinetics and tissue distribution was achieved across all species. In conclusion, the PBPK model developed based on a rich dataset obtained from mice, was able to reasonably predict the disposition of doxorubicin in other preclinical species and humans. Applicability of the model for special populations, such as patients with hepatic impairment, was also demonstrated. The proposed model will be a valuable tool for optimization of exposure profiles of doxorubicin in human patients. 相似文献
45.
46.
47.
48.
49.
Ekaterina S. Prokudina Boris K. Kurbatov Konstantin V. Zavadovsky Alexander V. Vrublevsky Natalia V. Naryzhnaya Yuri B. Lishmanov Leonid N. Maslov Peter R. Oeltgen 《Current Cardiology Reviews》2021,17(2):188
The purpose of the review is the analysis of clinical and experimental data on the etiology and pathogenesis of takotsubo syndrome (TS). TS is characterized by contractile dysfunction, which usually affects the apical region of the heart without obstruction of coronary artery, moderate increase in myocardial necrosis markers, prolonged QTc interval (in 50% of patients), sometimes elevation of ST segment (in 19% of patients), increase N-Terminal Pro-B-Type Natriuretic Peptide level, microvascular dysfunction, sometimes spasm of the epicardial coronary arteries (in 10% of patients), myocardial edema, and life-threatening ventricular arrhythmias (in 11% of patients). Stress cardiomyopathy is a rare disease, it is observed in 0.6 - 2.5% of patients with acute coronary syndrome. The occurrence of takotsubo syndrome is 9 times higher in women, who are aged 60-70 years old, than in men. The hospital mortality among patients with TS corresponds to 3.5% - 12%. Physical or emotional stress do not precede disease in all patients with TS. Most of patients with TS have neurological or mental illnesses. The level of catecholamines is increased in patients with TS, therefore, the occurrence of TS is associated with excessive activation of the adrenergic system. The negative inotropic effect of catecholamines is associated with the activation of β2 adrenergic receptors. An important role of the adrenergic system in the pathogenesis of TS is confirmed by studies which were performed using 125I-metaiodobenzylguanidine (125I -MIBG). TS causes edema and inflammation of the myocardium. The inflammatory response in TS is systemic. TS causes impaired coronary microcirculation and reduces coronary reserve. There is a reason to believe that an increase in blood viscosity may play an important role in the pathogenesis of microcirculatory dysfunction in patients with TS. Epicardial coronary artery spasm is not obligatory for the occurrence of TS. Cortisol, endothelin-1 and microRNAs are challengers for the role of TS triggers. A decrease in estrogen levels is a factor contributing to the onset of TS. The central nervous system appears to play an important role in the pathogenesis of TS. 相似文献
50.
Galyna V. Grygoriv Dmitry A. Lega Valentin P. Chernykh Lucjusz Zaprutko Andrzej K. Gzella Anna Paweczyk Leonid A. Shemchuk 《RSC advances》2018,8(65):37295
The reactivity of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide was studied in multicomponent type reactions for the first time, namely, in a three-component interaction with active methylene nitriles and aromatic aldehydes in order to construct condensed 2-amino-4H-pyran derivatives. The reaction outcome strongly depended on the nature of an active methylene nitrile and an arenecarbaldehyde. Application of malononitrile resulted in novel 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carbonitrile 5,5-dioxides in most cases, whereas the utilization of ethyl cyanoacetate resulted in a complex mixture of products. In the last case, three different products were isolated depending on the arenecarbaldehyde used, namely ethyl 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carboxylate 5,5-dioxides, ethyl 2-cyano-3-arylacrylates, and salts of 3,3′-(arylmethylene)bis(4-hydroxybenzo[e][1,2]oxathiine 2,2-dioxides). Attempts to obtain separately ethyl 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carboxylate 5,5-dioxides enabled us to propose reaction pathways leading to these products. The salts were obtained for the first time. The preparative method for the synthesis of triethylammonium salts of 3,3′-(arylmethylene)bis(4-hydroxybenzo[e][1,2]oxathiine 2,2-dioxides) was proposed by the direct interaction of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide with arenecarbaldehydes. The application of ammonium acetate as a catalyst allowed us to synthesize 7-aryl-7,14-dihydrobenzo[5,6][1,2]oxathiino[4,3-b]benzo[5,6][1,2]oxathiino[3,4-e]pyridine 6,6,8,8-tetraoxides containing a novel heterocyclic system. These facts, combined with our past investigations, allowed us to assert that the reactivity of enol nucleophiles that include the COCH2SO2X fragment has not been reported previously.Reactivity of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide was for the first time studied in multicomponent type reactions involving active methylene nitriles and aromatic aldehydes. 相似文献