全文获取类型
收费全文 | 7726篇 |
免费 | 701篇 |
国内免费 | 24篇 |
专业分类
耳鼻咽喉 | 63篇 |
儿科学 | 231篇 |
妇产科学 | 133篇 |
基础医学 | 1134篇 |
口腔科学 | 142篇 |
临床医学 | 901篇 |
内科学 | 1616篇 |
皮肤病学 | 343篇 |
神经病学 | 630篇 |
特种医学 | 330篇 |
外国民族医学 | 2篇 |
外科学 | 830篇 |
综合类 | 98篇 |
一般理论 | 13篇 |
预防医学 | 768篇 |
眼科学 | 196篇 |
药学 | 610篇 |
中国医学 | 12篇 |
肿瘤学 | 399篇 |
出版年
2022年 | 42篇 |
2021年 | 135篇 |
2020年 | 98篇 |
2019年 | 114篇 |
2018年 | 157篇 |
2017年 | 121篇 |
2016年 | 128篇 |
2015年 | 139篇 |
2014年 | 163篇 |
2013年 | 270篇 |
2012年 | 341篇 |
2011年 | 362篇 |
2010年 | 211篇 |
2009年 | 187篇 |
2008年 | 329篇 |
2007年 | 377篇 |
2006年 | 335篇 |
2005年 | 352篇 |
2004年 | 363篇 |
2003年 | 320篇 |
2002年 | 306篇 |
2001年 | 267篇 |
2000年 | 288篇 |
1999年 | 221篇 |
1998年 | 127篇 |
1997年 | 92篇 |
1996年 | 91篇 |
1995年 | 75篇 |
1994年 | 74篇 |
1993年 | 60篇 |
1992年 | 181篇 |
1991年 | 164篇 |
1990年 | 169篇 |
1989年 | 176篇 |
1988年 | 152篇 |
1987年 | 138篇 |
1986年 | 133篇 |
1985年 | 111篇 |
1984年 | 99篇 |
1983年 | 73篇 |
1982年 | 58篇 |
1981年 | 55篇 |
1980年 | 46篇 |
1979年 | 74篇 |
1978年 | 61篇 |
1977年 | 62篇 |
1976年 | 49篇 |
1975年 | 58篇 |
1974年 | 42篇 |
1973年 | 54篇 |
排序方式: 共有8451条查询结果,搜索用时 171 毫秒
81.
Rheumatoid arthritis is a chronic and destructive autoimmune joint disease characterized by inflammation of synovial tissue of unknown aetiology. Studies on TCR genes expressed by infiltrating T cells in synovial tissues have attempted to identify mechanism and specificity of the recruitment. T cell infiltrate in rheumatoid arthritis appears to be an association of a polyclonal non specific infiltrate with dominant clones or clonotypes. T cell repertoire in synovial tissue is biased compared to peripheral blood but no TCR V gene can be identified as commonly over-used. Comparison of motifs found in the CDR3 region of dominant clones from different studies has currently failed to identified a commonly motif. The fact that a number of dominant clones or clonotypes is present in different joints and at different times of the disease suggests a selective expansion of T lymphocytes in rheumatoid arthritis synovial membrane. Further investigations are needed to characterize the specificity of these dominant clonotypes. 相似文献
82.
Sympathetic nerve activity and neurotransmitter release in humans: translation from pathophysiology into clinical practice 总被引:6,自引:0,他引:6
Esler M Lambert G Brunner-La Rocca HP Vaddadi G Kaye D 《Acta physiologica Scandinavica》2003,177(3):275-284
AIM: There has been a revolution in cardiovascular neuroscience in recent years with, in some cases, translation into clinical practice of the knowledge of pathophysiology gained through application of sympathetic nerve recording and catecholamine isotope dilution methodology. OBESITY-RELATED HYPERTENSION: An earlier hypothesis, based on findings in most models, was that weight gain in obesity is due in part to sympathetic nervous underactivity reducing thermogenesis. Microneurography and regional noradrenaline spillover measurements in human obesity have disproven this hypothesis, weakening the case for the use of beta3-adrenergic agonists to stimulate thermogenesis. Sympathetic nerve firing rates in post-ganglionic fibres directed to the skeletal muscle vasculature are increased, as is renal sympathetic tone, with a doubling of the spillover rate of noradrenaline from the kidneys. Given these findings, antiadrenergic antihypertensive drugs may be the preferred agents for obesity-related hypertension, but this has not been adequately tested. ESSENTIAL HYPERTENSION: Whether stress causes high blood pressure, previously hotly debated, has been under recent review by an Australian Government body, the Specialist Medical Review Council. Despite medicolegal implications, the ruling was that stress is one proven cause of hypertension. The judgment was reached after consideration of the epidemiological evidence, but in particular the described neural pathophysiology of essential hypertension: (a) persistent sympathetic nervous stimulation is commonly present, (b) suprabulbar projections of noradrenergic brainstem neurones are activated and (c) adrenaline is released as a cotransmitter in sympathetic nerves. These were taken to be biological markers of stress. CARDIAC FAILURE: At one time, the failing heart was thought to be sympathetically denervated. Longterm administration of inotropic adrenergic agonists, to provide the cardiac catecholamine stimulation thought to be lacking, increased mortality. Noradrenaline isotope dilution methodology subsequently demonstrated that the sympathetic outflow to the heart was preferentially activated, cardiac noradrenaline spillover being increased as much as 50-fold. The level of stimulation of the cardiac sympathetic nerves was the most powerful predictor of death. These observations provide the theoretical foundation for the very successful introduction of beta-adrenergic blockers for treatment of heart failure. 相似文献
83.
Whole-cell recordings of EPSCs and G-protein-activated inwardly rectifying (GIRK) currents were made from cultured hippocampal neurones to determine the effect of long-term agonist treatment on the presynaptic and postsynaptic responses mediated by GABAB receptors (GABAB Rs). GABAB R-mediated presynaptic inhibition was unaffected by agonist (baclofen) treatment for up to 48 h, and was desensitized by about one-half after 96 h. In contrast, GABAB R-mediated GIRK currents were desensitized by a similar amount after only 2 h of agonist treatment. In addition, presynaptic inhibition mediated by A1 adenosine receptors (A1 Rs) was unaffected by prolonged GABAB R activation, whereas A1 R-mediated GIRK currents were desensitized. Desensitization of postsynaptic GABAB R and A1 R responses was blocked by the GABAB R antagonist (1-(S)-3,4-dichlorophenylethyl)amino-2-(S) hydroxypropyl-p-benzyl-phosphonic acid (CGP 55845A), but not by the A1 R antagonist cyclopentyldipropylxanthine (DPCPX). GIRK current amplitude could be partially restored after baclofen treatment by either coapplication of baclofen and adenosine, or intracellular infusion of the non-hydrolysable GTP analog 5'-guanylylimidodiphosphate (Gpp(NH)p). Short-term (4-24 h) baclofen treatment also significantly desensitized the inhibition of postsynaptic voltage-gated calcium channels by activation of GABAB Rs or A1 Rs. These results show that responses mediated by GABAB Rs and A1 Rs desensitize differently in presynaptic and postsynaptic compartments, and demonstrate the heterologous desensitization of postsynaptic A1R responses. 相似文献
84.
85.
Interleukin-2 induced immune effects in human immunodeficiency virus-infected patients receiving intermittent interleukin-2 immunotherapy 总被引:4,自引:0,他引:4
Kovacs JA Vogel S Metcalf JA Baseler M Stevens R Adelsberger J Lempicki R Hengel RL Sereti I Lambert L Dewar RL Davey RT Walker RE Falloon J Polis MA Masur H Lane HC 《European journal of immunology》2001,31(5):1351-1360
To characterize the immunological effects of intermittent IL-2 therapy, which leads to selective increases in CD4+ T lymphocytes in HIV-infected patients, 11 patients underwent extensive immunological evaluation. While IL-2 induced changes in both CD4+ and CD8+ cell number acutely, only CD4+ cells showed sustained increases following discontinuation of IL-2. Transient increases in expression of the activation markers CD38 and HLA-DR were seen on both CD4+ and CD8+ cells, but CD25 (a chain of the IL-2 receptor) increased exclusively on CD4+ cells. This increase in CD25 expression was sustained for months following discontinuation of IL-2, and was seen in naive as well as memory cells. IL-2 induced cell proliferation, but tachyphylaxis to these proliferative effects developed after 1 week despite continued IL-2 administration. It thus appears that sustained CD25 expression selectively on CD4+ cells is a critical component of the immunological response to IL-2, and that intermittent administration of IL-2 is necessary to overcome the tachyphylaxis to IL-2-induced proliferation. 相似文献
86.
Involvement of tumour necrosis factor and other cytokines in immune-mediated vascular pathology 总被引:6,自引:0,他引:6
G E Grau P F Piguet P Vassalli P H Lambert 《International archives of allergy and applied immunology》1989,88(1-2):34-39
Vascular endothelial cells are actively involved in coagulation and inflammation processes and appear to represent an important element in cell-mediated immune responses. In this paper, the possible role of endothelial cells as a target for immunopathological reactions was analyzed. Experimental neurovascular lesions were studied in a model of cerebral malaria, with particular attention to the role of cytokine interactions in vivo. 相似文献
87.
88.
M. A. Livesley S. E. Tebbs H. A. Moss M. H. Faroqui P. A. Lambert T. S. J. Elliott 《European journal of clinical microbiology & infectious diseases》1998,17(2):108-112
Microorganisms detected in situ on the distal tip of central venous catheters (CVC) within 90 min of insertion were investigated using pulsed-field gel electrophoresis to analyse genomic fragments obtained with theSmaI restriction enzyme. Thirty patients received a triple lumen CVC, which was inserted directly through the skin using the Seldinger technique. In a further 30 patients a triple lumen CVC was inserted through a Swan sheath, thereby avoiding direct contact of the CVC with the skin. Staphylococci were isolated from the distal tips of the catheters in 6 patients (5 who had the CVC inserted directly through the skin and 1 who had the CVC inserted via a Swan sheath.) Twenty-three staphylococcal isolates were also isolated from the insertion equipment and the skin swabs surrounding the insertion site of these six patients. All the isolates were genotyped. In one of the patients the organisms isolated from the skin were identical to those on the CVC tip. In two further patients similar organisms were isolated from the insertion equipment and the patients' skin. These results, in addition to the reduced colonisation rates observed when catheters were introduced through a Swan sheath, support the hypothesis that microorganisms from the skin are impacted onto the CVC tip and the CVC insertion equipment at catheter insertion. 相似文献
89.
Linda C. Lambert Hoa Q. Trummell Ashvani Singh Gail H. Cassell Robert J. Bridges 《Infection and immunity》1998,66(1):272-279
Murine chronic respiratory disease is characterized by persistent colonization of tracheal and bronchial epithelial cell surfaces by Mycoplasma pulmonis, submucosal and intraluminal immune and inflammatory cells, and altered airway activity. To determine the direct effect of M. pulmonis upon transepithelial ion transport in the absence of immune and inflammatory cell responses, primary mouse tracheal epithelial cell monolayers (MTEs) were apically infected and assayed in Ussing chambers. M. pulmonis-infected MTEs, but not those infected with a nonmurine mycoplasma, demonstrated reductions in amiloride-sensitive Na+ absorption, cyclic AMP, and cholinergic-stimulated Cl− secretion and transepithelial resistance. These effects were shown to require interaction of viable organisms with the apical surface of the monolayer and to be dependent upon organism number and duration of infection. Altered transport due to M. pulmonis was not merely a result of epithelial cell death as evidenced by the following: (i) active transport of Na+ and Cl−, albeit at reduced rates; (ii) normal cell morphology, including intact tight junctions, as demonstrated by electron microscopy; (iii) maintenance of a mean transepithelial resistance of 440 Ω/cm2; and (iv) lack of leakage of fluid from the basolateral to the apical surface of the monolayer. Alteration in epithelial ion transport in vitro is consistent with impaired pulmonary clearance and altered airway function in M. pulmonis-infected animals. Furthermore, the ability of M. pulmonis to alter transport without killing the host cell may explain its successful parasitism and long-term persistence in the host. Further study of the MTE-M. pulmonis model should elucidate the molecular mechanisms which mediate this reduction in transepithelial ion transport.Mycoplasmas, the smallest free-living prokaryotes, continue to be a significant cause of respiratory infections in a variety of animals, including humans (44). Their limited biosynthetic capability dictates that these organisms must both colonize and parasitize epithelial cell surfaces. It is therefore surprising that mycoplasmas produce diseases that are slowly progressing and chronic and yet often clinically inconspicuous. The molecular mechanisms responsible for this tenuous truce between the pathogen and the host cell have not yet been identified. Murine respiratory mycoplasmosis, a naturally occurring respiratory disease in laboratory rats and mice caused by Mycoplasma pulmonis (6, 8) and characterized by chronic, often lifelong tracheitis, bronchopneumonia, and bronchiectasis (7, 23, 28), would seem to be an ideal model with which to study these mechanisms. Although M. pulmonis-infected animals generate intense local and systemic immune responses (24, 33, 42, 43), they are incapable of eliminating the organism from the respiratory epithelium. Remodeling of the airways typically observed in infected animals, impairment of pulmonary clearance, and accumulation of mucus (23) suggest that M. pulmonis may compromise the ability of the epithelial cells to absorb and secrete fluid and electrolytes.Airway epithelial cells possess two major active transport processes, Na+ absorption and Cl− section. Water, in turn, osmotically follows the transepithelial movement of these ions, thereby providing a fluid film between the mucus layer and the epithelial cell surface. The depth and composition of this fluid microenvironment must be carefully regulated to allow the exchange of gases and the humidification of the airway epithelium and to ensure proper mucociliary clearance (47, 49). The consequences of impaired fluid and electrolyte transport in the airways are strikingly apparent in cases of cystic fibrosis, a recessive genetic disease resulting from the loss of epithelial chloride channels (31, 48). The studies reported here were designed to determine whether M. pulmonis infection alters electrolyte transport across the murine tracheal epithelium.The effect of bacteria upon mammalian epithelia in the absence of immune and inflammatory cells can be systematically evaluated by using the Ussing chamber model. Short-circuit current (Isc) studies have helped determine the mechanism by which cholera toxin (18) and other enterotoxins affect the intestinal mucosa (17, 35). Study of various types of epithelial cells by using the Ussing chamber model has also resulted in the identification of numerous microbial substances capable of directly altering the ion transport capacity of the airway epithelium (3, 20, 41).In the present study, control and M. pulmonis-infected mouse tracheal epithelial cells (MTEs) were evaluated in Ussing chambers. The results clearly show that M. pulmonis infection directly alters epithelial ion transport and that this alteration is species specific, dose and time related, and dependent upon the association of viable organisms with the apical cell surface. 相似文献