全文获取类型
收费全文 | 13363篇 |
免费 | 705篇 |
国内免费 | 96篇 |
专业分类
耳鼻咽喉 | 88篇 |
儿科学 | 227篇 |
妇产科学 | 124篇 |
基础医学 | 2162篇 |
口腔科学 | 97篇 |
临床医学 | 1363篇 |
内科学 | 3017篇 |
皮肤病学 | 357篇 |
神经病学 | 1300篇 |
特种医学 | 523篇 |
外科学 | 2040篇 |
综合类 | 52篇 |
一般理论 | 2篇 |
预防医学 | 657篇 |
眼科学 | 215篇 |
药学 | 929篇 |
中国医学 | 40篇 |
肿瘤学 | 971篇 |
出版年
2023年 | 63篇 |
2022年 | 84篇 |
2021年 | 260篇 |
2020年 | 151篇 |
2019年 | 223篇 |
2018年 | 318篇 |
2017年 | 202篇 |
2016年 | 237篇 |
2015年 | 269篇 |
2014年 | 372篇 |
2013年 | 515篇 |
2012年 | 903篇 |
2011年 | 1023篇 |
2010年 | 605篇 |
2009年 | 536篇 |
2008年 | 872篇 |
2007年 | 1012篇 |
2006年 | 908篇 |
2005年 | 943篇 |
2004年 | 879篇 |
2003年 | 865篇 |
2002年 | 845篇 |
2001年 | 138篇 |
2000年 | 106篇 |
1999年 | 149篇 |
1998年 | 214篇 |
1997年 | 165篇 |
1996年 | 164篇 |
1995年 | 110篇 |
1994年 | 111篇 |
1993年 | 110篇 |
1992年 | 99篇 |
1991年 | 65篇 |
1990年 | 51篇 |
1989年 | 65篇 |
1988年 | 57篇 |
1987年 | 46篇 |
1986年 | 48篇 |
1985年 | 39篇 |
1984年 | 48篇 |
1983年 | 41篇 |
1982年 | 42篇 |
1981年 | 33篇 |
1980年 | 36篇 |
1979年 | 24篇 |
1978年 | 22篇 |
1977年 | 16篇 |
1976年 | 10篇 |
1975年 | 10篇 |
1974年 | 17篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
Stephane Palazzetti Marie-Jeanne Richard Alain Favier Irene Margaritis 《Revue canadienne de physiologie appliquée》2003,28(4):588-604
We hypothesized that overloaded training (OT) in triathlon would induce oxidative stress and damage on muscle and DNA. Nine male triathletes and 6 male sedentary subjects participated in this study. Before and after a 4-week OT, triathletes exercised for a duathlon. Blood ratio of reduced vs. oxidized glutathione (GSH/GSSG), plasma thiobarbituric acid reactive substances (TBARS), leukocyte DNA damage, creatine kinase (CK), and CK-MB mass in plasma, erythrocyte superoxide dismutase (SOD) activity, erythrocyte and plasma glutathione peroxidase (GSH-Px) activities, and plasma total antioxidant status (TAS) were measured before and after OT in pre- and postexercise situations. Triathletes were overloaded in response to OT. In rest conditions, OT induced plasma GSH-Px activity increase and plasma TAS decrease (both p < 0.05). In exercise conditions, OT resulted in higher exercise-induced variations of blood GSH/GSSG ratio, TBARS level (both p < 0.05), and CK-MB mass (p < 0.01) in plasma; and decreased TAS response (p < 0.05). OT could compromise the antioxidant defense mechanism with respect to exercise-induced response. The resulting increased exercise-induced oxidative stress and further cellular susceptibility to damage needs more study. 相似文献
102.
Piracy of Decay-Accelerating Factor (CD55) Signal Transduction by the Diffusely Adhering Strain Escherichia coli C1845 Promotes Cytoskeletal F-Actin Rearrangements in Cultured Human Intestinal INT407 Cells 总被引:2,自引:0,他引:2 下载免费PDF全文
Isabelle Peiffer Alain L. Servin Marie-Franoise Bernet-Camard 《Infection and immunity》1998,66(9):4036-4042
Diffusely adhering Escherichia coli (DAEC) C1845 (clinical isolate) harboring the fimbrial adhesin F1845 can infect cultured human differentiated intestinal epithelial cells; this process is followed by the disassembly of the actin network in the apical domain. The aim of this study was to examine the mechanism by which DAEC C1845 promotes F-actin rearrangements. For this purpose, we used a human embryonic intestinal cell line (INT407) expressing the membrane-associated glycosylphosphatidylinositol (GPI) protein-anchored decay-accelerating factor (DAF), the receptor of the F1845 adhesin. We show here that infection of INT407 cells by DAEC C1845 can provoke dramatic F-actin rearrangements without cell entry. Clustering of phosphotyrosines was observed, revealing that the DAEC C1845-DAF interaction involves the recruitment of signal transduction molecules. A pharmacological approach with a subset of inhibitors of signal transduction molecules was used to identify the cascade of signal transduction molecules that are coupled to the DAF, that are activated upon infection, and that promote the F-actin rearrangements. DAEC C1845-induced F-actin rearrangements can be blocked dose dependently by protein tyrosine kinase, phospholipase Cγ, phosphatidylinositol 3-kinase, protein kinase C, and Ca2+ inhibitors. F-actin rearrangements and blocking by inhibitors were observed after infection of the cells with two E. coli recombinants carrying the plasmids containing the fimbrial adhesin F1845 or the fimbrial hemagglutinin Dr, belonging to the same family of adhesins. These findings show that the DAEC Dr family of pathogens promotes alterations in the intestinal cell cytoskeleton by piracy of the DAF-GPI signal cascade without bacterial cell entry. 相似文献
103.
Bernard Levy Alain Ghaem Jeanne Marie Verpillat Jean Paul Martineaud 《Pflügers Archiv : European journal of physiology》1975,359(1-2):137-146
Measurements were made in man of heart rate (Fc), arterial blood pressure (Pa), cutaneous blood flow (Z) (by plethysmography of the hand) as well as variation sin venous volume (deltaV) in the course of muscular exercise of 70 Watts intensity corresponding from 48% to 60% of the maximal oxygen consumtion of the subjects. These exercises were carried out at ambient temperatures of 22 degrees and 29 degrees C. for 8 min. In every case, an initial lowering of the Q and deltaV followed by a progressive climb was found. The average maximal reduction in output was virtually identical at 22 degrees and 29 degrees C (4.10 +/- 2.05 and 4.00 +/- 2.31 ml/min. 100 cm3). But the average maximal fall in volume turned out to be less at 29 degrees C (0.30 +/- 0.40 ml/100 cm3) than at 22 degrees C (0.60 +/- 0.60 ml/100 cm3). The resistive sector of cutaneous circulation conserves the same vasomotor capacities at the two ambient temperatures studied; the cutaneous capacitive sector shows lower reactivity at the higher ambient temperature. This would suggest that diminished venous return may be partially responsible for poor tolerance to exercise in warm climates. 相似文献
104.
105.
106.
Molina TJ Delmer A Cymbalista F Le Tourneau A Perrot JY Ramond S Marie JP Audouin J Zittoun R Diebold J 《Virchows Archiv : an international journal of pathology》2000,437(6):591-598
Mantle cell lymphoma (MCL) is a well-defined peripheral B-cell lymphoma usually diagnosed upon peripheral lymph node biopsy. We report eight cases of peripheral B-cell leukaemia that demonstrate presumptive evidence of mantle cell characteristics. The patients had a median age of 68.5 years, and five were male. All presented with an enlarged spleen without any peripheral lymphadenopathies, and they were leukaemic at presentation (median lymphocytosis, 38x10(9)/l). Morphological diagnosis of MCL was very difficult in five cases but easier in three because we were able to analyse either pre- or post-mortem lymph nodes and spleen. The immunophenotype of blood lymphocytosis using flow cytometry, the presence of a t(11;14)(q13;q32) and a cyclin D1 expression by leukaemic cells all fit with the diagnosis of MCL. All patients progressed and died with a median overall survival of 8 months. Multifocal areas of transformation in blastoid or large cell variants were observed in the three autopsied patients. In summary, one should consider the diagnosis of MCL at presentation in leukaemic phase even in the absence of peripheral adenopathies. 相似文献
107.
Xavier Sastre‐Garau Jrme Couturier Josette Derr Alain Aurias Jerzy Klijanienko Ral Lagac 《The Journal of pathology》2002,196(1):97-102
Inflammatory myofibroblastic tumours (IMTs) were initially considered to be benign reactive processes, but cases with an unfavourable outcome have been reported. Moreover, clonal genetic alterations have recently been published in some cases, suggesting that IMT may represent a malignant neoplastic entity. This paper reports a case of IMT that developed in the mammary gland, an unusual site. The histological picture was characterized by a proliferation of spindle cells with little cellular atypia and rare mitoses, associated with a polymorphous inflammatory infiltrate. Their immunophenotype, characterized by the expression of vimentin, smooth muscle actin, and cytokeratins, corresponded to that of myofibroblasts. Cytogenetic analysis revealed the clonal nature of the lesion. The modal karyotype was 48, X, ins(2;X)(q34;p21.2p22.2), +7, del(9)(p23), +19. Including the present observation, a 9p deletion has now been found in three cases of IMT. These observations show that IMT may be a clonal neoplasm, even in sites different from deep soft tissues. 相似文献
108.
Claire Bihoreau Agns Heurtier Alain Enjalbert Nicole Corvaïa Armand Bensussan Laurent Degos Claude Kordon 《European journal of immunology》1991,21(11):2877-2882
A monoclonal antibody (OKT3) directed against the T cell receptor (TcR)/CD3 molecular complex, as well as a protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate, PMA) were added to a culture of tumoral Jurkat T cells, in order to precise the sequence of intracellular signals leading to T cell activation. The experiments were performed in the presence or in absence of various stimulators of adenylate cyclase (AC) such as forskolin (FK), cholera toxin (CT) or prostaglandin E2 (PGE2). OKT3 increased inositol phosphate (IP) production; in parallel, it induced a slight accumulation of cAMP. The effect was markedly potentiated in presence of FK or CT, and to a lesser extent in the presence of PGE2. FK stimulated adenylate cyclase of Jurkat cell membranes, but the effect was not potentiated by OKT3, suggesting that potentiation of cAMP accumulation requires intact cells and is not mediated by direct receptor coupling. On the other hand, elevated cAMP accumulation induced a negative feedback on IP production. The effect of OKT3 on cAMP was mimicked by A23187, a Ca2+ ionophore, and abolished in the absence of extracellular Ca2+. PMA had the same effect as OKT3 on basal or FK- and CT-induced accumulation of cAMP. In contrast, it inhibited the PGE2 effect on the cyclic nucleotide. After desensitization of PKC by pretreatment with a high concentration of PMA, the phorbol ester was no longer effective. Under those conditions, facilitation by OKT3 of FK-induced accumulation of cAMP was preserved, whereas potentiation by the monoclonal antibody of the PGE2 stimulation of AC was even enhanced. The data indicate that cAMP accumulation indirectly elicited by phospholipase C activation is, at least partly, mediated by IP-dependent Ca2+ mobilization, while PKC is preferentially effective as an inhibitor of PGE2 stimulation. 相似文献
109.
Quantification of human basophils and their degranulation were performed using a flow-cytometric system. It was shown that the number of basophils among total leukocytes, before and after the effect of degranulating agents, can be obtained rapidly and reproducibly, following alcian blue, staining. Dose-response curves of degranulation by anti-IgE and anti-IgG4 were studied, and it was shown that these antibodies can induce basophil degranulation in a Ca++ dependent manner. It was also shown that degranulation is completed within 10 min.
Values obtained by flow-cytometry and microscopic evaluation, as well as comparison made between percent basophil degranulation and percent histamine release, agreed well with each other in our system. Flow-cytometric analysis of human basophil degranulation provides a new reliable method to assess in vitro the morphological basis of immediate hyper-sensitivity. 相似文献
Values obtained by flow-cytometry and microscopic evaluation, as well as comparison made between percent basophil degranulation and percent histamine release, agreed well with each other in our system. Flow-cytometric analysis of human basophil degranulation provides a new reliable method to assess in vitro the morphological basis of immediate hyper-sensitivity. 相似文献
110.
Créange A 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》2000,14(1):1-11
Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating neuropathy that is associated with long-lasting morbidity and a substantial risk of mortality. The 2 reference treatments, plasma exchange and intravenous immunoglobulins (IVIg), do not change the functional prognosis for the most severely ill patients. The pathogenesis of GBS involves humoral and cellular immune dysfunctions that have only recently been characterised. Antibodies to nerve antigens may participate in complement activation, antibody-dependent macrophage cytotoxicity and reversible conduction failure. The cellular immune reaction is associated with increases in pro-inflammatory cytokines [such as tumour necrosis factor-alpha (TNFalpha)] and matrix metalloproteinases (MMPs; e.g. MMP-9), and a decrease in anti-inflammatory cytokines [such as transforming growth factor-beta1 (TGFbeta1)]. All the changes favour adhesion to and transmigration across the endothelium of immune cells, a key phenomenon associated with GBS. Recovery from GBS is characterised by the normalisation of these changes. Experimental allergic neuritis (EAN), the experimental model of GBS, has strikingly similar immunological characteristics. The usual treatment options for patients with GBS (plasma exchange and IVIg) mainly target the humoral component of the immune response. Interferon-beta (IFNbeta) is a cellular immunomodulator that inhibits antigen presentation and TNFalpha production and binding, and modulates macrophage properties. IFNbeta increases anti-inflammatory T cell functions and the production of anti-inflammatory cytokines, such as TGFbeta1. IFNbeta has important effects on leukodiapedesis, caused by modulating the expression of cell adhesion molecules and the MMP-9 proteinases. It has been used with success in EAN, in some patients with acute exacerbation of chronic inflammatory demyelinating polyneuropathy, and in 1 patient with GBS. The pathophysiology of patients with GBS, an understanding of IFNbeta properties and results of experimental studies support the investigation of IFNbeta in trials of patients with GBS. 相似文献