全文获取类型
收费全文 | 1327篇 |
免费 | 98篇 |
国内免费 | 9篇 |
专业分类
耳鼻咽喉 | 23篇 |
儿科学 | 14篇 |
妇产科学 | 21篇 |
基础医学 | 188篇 |
口腔科学 | 8篇 |
临床医学 | 135篇 |
内科学 | 284篇 |
皮肤病学 | 18篇 |
神经病学 | 144篇 |
特种医学 | 81篇 |
外科学 | 261篇 |
综合类 | 3篇 |
预防医学 | 79篇 |
眼科学 | 7篇 |
药学 | 84篇 |
肿瘤学 | 84篇 |
出版年
2024年 | 3篇 |
2023年 | 10篇 |
2022年 | 36篇 |
2021年 | 50篇 |
2020年 | 34篇 |
2019年 | 64篇 |
2018年 | 64篇 |
2017年 | 35篇 |
2016年 | 48篇 |
2015年 | 54篇 |
2014年 | 81篇 |
2013年 | 84篇 |
2012年 | 134篇 |
2011年 | 136篇 |
2010年 | 89篇 |
2009年 | 49篇 |
2008年 | 103篇 |
2007年 | 83篇 |
2006年 | 70篇 |
2005年 | 53篇 |
2004年 | 43篇 |
2003年 | 36篇 |
2002年 | 28篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1993年 | 3篇 |
1991年 | 3篇 |
1989年 | 2篇 |
1988年 | 6篇 |
1987年 | 1篇 |
1986年 | 4篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1977年 | 3篇 |
1974年 | 2篇 |
1972年 | 1篇 |
排序方式: 共有1434条查询结果,搜索用时 15 毫秒
21.
Andrea L. Frump Marjorie Albrecht Bakhtiyor Yakubov Sandra Breuils-Bonnet Valrie Nadeau Eve Tremblay Francois Potus Junichi Omura Todd Cook Amanda Fisher Brooke Rodriguez R. Dale Brown Kurt R. Stenmark C. Dustin Rubinstein Kathy Krentz Diana M. Tabima Rongbo Li Xin Sun Naomi C. Chesler Steeve Provencher Sebastien Bonnet Tim Lahm 《The Journal of clinical investigation》2021,131(6)
Women with pulmonary arterial hypertension (PAH) exhibit better right ventricular (RV) function and survival than men; however, the underlying mechanisms are unknown. We hypothesized that 17β-estradiol (E2), through estrogen receptor α (ER-α), attenuates PAH-induced RV failure (RVF) by upregulating the procontractile and prosurvival peptide apelin via a BMPR2-dependent mechanism. We found that ER-α and apelin expression were decreased in RV homogenates from patients with RVF and from rats with maladaptive (but not adaptive) RV remodeling. RV cardiomyocyte apelin abundance increased in vivo or in vitro after treatment with E2 or ER-α agonist. Studies employing ER-α–null or ER-β–null mice, ER-α loss-of-function mutant rats, or siRNA demonstrated that ER-α is necessary for E2 to upregulate RV apelin. E2 and ER-α increased BMPR2 in pulmonary hypertension RVs and in isolated RV cardiomyocytes, associated with ER-α binding to the Bmpr2 promoter. BMPR2 is required for E2-mediated increases in apelin abundance, and both BMPR2 and apelin are necessary for E2 to exert RV-protective effects. E2 or ER-α agonist rescued monocrotaline pulmonary hypertension and restored RV apelin and BMPR2. We identified what we believe to be a novel cardioprotective E2/ER-α/BMPR2/apelin axis in the RV. Harnessing this axis may lead to novel RV-targeted therapies for PAH patients of either sex. 相似文献
22.
Colin J. Mahoney Ian B. Malone Gerard R. Ridgway Aisling H. Buckley Laura E. Downey Hannah L. Golden Natalie S. Ryan Sebastien Ourselin Jonathan M. Schott Martin N. Rossor Nick C. Fox Jason D. Warren 《Neurobiology of aging》2013
The primary progressive aphasias (PPA) are a heterogeneous group of language-led neurodegenerative diseases resulting from large-scale brain network degeneration. White matter (WM) pathways bind networks together, and might therefore hold information about PPA pathogenesis. Here we used diffusion tensor imaging and tract-based spatial statistics to compare WM tract changes between PPA syndromes and with respect to Alzheimer's disease and healthy controls in 33 patients with PPA (13 nonfluent/agrammatic PPA); 10 logopenic variant PPA; and 10 semantic variant PPA. Nonfluent/agrammatic PPA was associated with predominantly left-sided and anterior tract alterations including uncinate fasciculus (UF) and subcortical projections; semantic variant PPA with bilateral alterations in inferior longitudinal fasciculus and UF; and logopenic variant PPA with bilateral but predominantly left-sided alterations in inferior longitudinal fasciculus, UF, superior longitudinal fasciculus, and subcortical projections. Tract alterations were more extensive than gray matter alterations, and the extent of alteration across tracts and PPA syndromes varied between diffusivity metrics. These WM signatures of PPA syndromes illustrate the selective vulnerability of brain language networks in these diseases and might have some pathologic specificity. 相似文献
23.
Pierre Frange David Boutolleau Marianne Leruez-Ville Fabien Touzot Guilhem Cros Sebastien Heritier Despina Moshous Benedicte Neven Alain Fischer Stephane Blanche 《Journal of clinical microbiology》2013,51(12):4266-4269
We describe a case of antiviral-resistant cytomegalovirus meningoencephalitis occurring after hematopoietic stem cell transplantation. Antiviral-resistant cytomegalovirus was identified in blood 16 months earlier. However, wild-type cytomegalovirus was evidenced in blood when the meningoencephalitis was diagnosed. Treatment of meningoencephalitis should be adapted to all previously identified resistance mutations in any compartment. 相似文献
24.
Strazzulla Alessio Postorino Maria Concetta Youbong Tracie Rouyer Maxence Flateau Clara Chakvetadze Catherine de Pontfarcy Astrid Pitsch Aurelia Jochmans Sebastien Belfeki Nabil Monchi Mehran Diamantis Sylvain 《European journal of clinical microbiology & infectious diseases》2021,40(7):1511-1516
European Journal of Clinical Microbiology & Infectious Diseases - This is a subanalysis of a previous study which compared the effectiveness of trimetoprim-sulfametoxazole (TMP-SMX) with all... 相似文献
25.
Xinting Yu Mirja Quante Michael Rueschman Tayla Ash Emily R Kaplan Na Guo Christine M Horan Sebastien Haneuse Kirsten Davison Elsie M Taveras Susan Redline 《Sleep》2021,44(3)
Study ObjectivesTo characterize objectively assessed sleep–wake patterns in infants at approximately 1 month and 6 months and examine the differences among infants with different racial/ethnic backgrounds and household socioeconomic status (SES).MethodsFull-term healthy singletons wore an ankle-placed actigraph at approximately 1 month and 6 months and parents completed sleep diaries. Associations of racial/ethnic and socioeconomic indices with sleep outcomes were examined using multivariable analyses. Covariates included sex, birth weight for gestational age z-score, age at assessment, maternal education, household income, bed-sharing, and breastfeeding.ResultsThe sample included 306 infants, of whom 51% were female, 42.5% non-Hispanic white, 32.7% Hispanic, 17.3% Asian, and 7.5% black. Between 1 month and 6 months, night sleep duration increased by 65.7 minutes (95% CI: 55.4, 76.0), night awakenings decreased by 2.2 episodes (2.0, 2.4), and daytime sleep duration decreased by 73.3 minutes (66.4, 80.2). Compared to change in night sleep duration over this development period for white infants (82.3 minutes [66.5, 98.0]), night sleep increased less for Hispanic (48.9 minutes [30.8, 66.9]) and black infants (31.6 minutes [−5.9, 69.1]). Night sleep duration also increased less for infants with lower maternal education and household income. Asian infants had more frequent night awakenings. Adjustment for maternal education and household income attenuated all observed day and night sleep duration differences other than in Asians, where persistently reduced nighttime sleep at 6 months was observed.ConclusionsRacial/ethnic differences in sleep emerge in early infancy. Night and 24-hour sleep durations increase less in Hispanic and black infants compared to white infants, with differences largely explained by SES. 相似文献
26.
27.
28.
Activation of p38 mitogen-activated protein kinase contributes to the early cardiodepressant action of tumor necrosis factor. 总被引:1,自引:0,他引:1
Mohamed Bellahcene Sebastien Jacquet Xue B Cao Masaya Tanno Robert S Haworth Joanne Layland Alamgir M Kabir Matthias Gaestel Roger J Davis Richard A Flavell Ajay M Shah Metin Avkiran Michael S Marber 《Journal of the American College of Cardiology》2006,48(3):545-555
OBJECTIVES: The purpose of this study was to determine whether p38 mitogen-activated protein kinase (p38-MAPK) contributes to tumor necrosis factor-alpha (TNFalpha)-induced contractile depression. BACKGROUND: Tumor necrosis factor has both beneficial and detrimental consequences that may result from the activation of different downstream pathways. Tumor necrosis factor activates p38-MAPK, a stress-responsive kinase implicated in contractile depression and cardiac injury. METHODS: In isolated hearts from mice lacking the p38-MAPK activator, MAPK kinase 3 (MKK3), perfused at constant coronary pressure or flow, we measured the left ventricular developed pressure (LVDP) and the relationship between end-diastolic volume and LVDP in the presence and absence of 10 ng/ml TNFalpha. RESULTS: Within 15 min at constant pressure, TNFalpha significantly reduced LVDP and coronary flow in outbred and mkk3(+/+) mice. This early negative inotropic effect was associated with a marked phosphorylation of both p38-MAPK and its indirect substrate, HSP27. In hearts lacking MKK3, TNFalpha failed to activate p38-MAPK or to cause significant contractile dysfunction. The actions of TNFalpha were similarly attenuated in MAPK-activated protein kinase 2 (MK2)-deficient hearts, which have a marked reduction in myocardial p38-MAPK protein content, and by the p38-MAPK catalytic site inhibitor SB203580 (1 micromol/l). Under conditions of constant coronary flow, the p38-MAPK activation and contractile depression induced by TNFalpha, though attenuated, remained sensitive to the absence of MKK3 or the presence of SB203580. The role of p38-MAPK in TNFalpha-induced contractile depression was confirmed in isolated murine cardiac myocytes exposed to SB203580 or lacking MKK3. CONCLUSIONS: Tumor necrosis factor activates p38-MAPK in the intact heart and in isolated cardiac myocytes through MKK3. This activation likely contributes to the early cardiodepressant action of TNFalpha. 相似文献
29.
Poupon V Girard M Legendre-Guillemin V Thomas S Bourbonniere L Philie J Bright NA McPherson PS 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(1):168-173
Clathrin-coated vesicles (CCVs) are major carriers for endocytic cargo and mediate important intracellular trafficking events at the trans-Golgi network (TGN) and endosomes. Whereas clathrin heavy chain provides the structural backbone of the clathrin coat, the role of clathrin light chains (CLCs) is poorly understood. We now demonstrate that CLCs are not required for clathrin-mediated endocytosis but are critical for clathrin-mediated trafficking between the TGN and the endosomal system. Specifically, CLC knockdown (KD) causes the cation-independent mannose-6 phosphate receptor (CI-MPR) to cluster near the TGN leading to a delay in processing of the lysosomal hydrolase cathepsin D. A recently identified binding partner for CLCs is huntingtin-interacting protein 1-related (HIP1R), which is required for productive interactions of CCVs with the actin cytoskeleton. CLC KD causes mislocalization of HIP1R and overassembly of actin, which accumulates in patches around the clustered CI-MPR. A dominant-negative CLC construct that disrupts HIP1R/CLC interactions causes similar alterations in CI-MPR trafficking and actin assembly. Thus, in mammalian cells CLCs function in intracellular membrane trafficking by acting as recruitment proteins for HIP1R, enabling HIP1R to regulate actin assembly on clathrin-coated structures. 相似文献
30.