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61.
The adenosine agonist cyclohexaladenosine injected into the medial pontine reticular formation of the rat induces a long-lasting increase in rapid eye movement sleep. To investigate the adenosine receptor-subtype(s) mediating this effect, the dose-response relationships for increasing rapid eye movement sleep by two highly selective adenosine receptor agonists were compared. Rats were surgically prepared for chronic sleep recording and bilateral guide cannulae were aimed at medial sites in the caudal, oral pontine reticular formation. Injections were made unilaterally in 60 nl volumes within 1 h after lights-on. The adenosine agonists used were A1-selective cyclohexaladenosine (10(-6)-10(-4) M) and A2a-selective CGS 21680 (10(-7)-10(-3) M). Each animal also received a series of three, paired-consecutive injections of the muscarinic receptor antagonist atropine (4x10(-3) M) followed by the lowest effective dose of each agonist or saline as control. The A2a receptor agonist, CGS 21680, was one order of magnitude more potent than the A1 receptor agonist, cyclohexaladenosine, in inducing rapid eye movement sleep increases. Preinjection of atropine at a dose that did not itself affect rapid eye movement sleep resulted in antagonism of CGS 21680, but not cyclohexaladenosine-induced rapid eye movement sleep.The differential sensitivity of these ligands to antagonism by atropine supports the conclusion that both A1 and A2a adenosine receptor subtypes in the reticular formation subserve agonist-induced rapid eye movement sleep and that they do so by independent mechanisms. The A2a mechanism requires the cholinergic system and may act through the increased release of acetylcholine. The A1 mechanism operates at a different locus possibly through an inhibition of GABA neurotransmission. 相似文献
62.
Dr. Michael S. Marks 《Immunologic research》1998,17(1-2):141-154
Major histocompatibility complex (MHC) class II molecules are required for the presentation of antigenic peptides that are
derived predominantly from internalized proteins. The assembly of MHC class II/peptide complexes occurs within endosomal compartments
of antigen-presenting cells (APCs). Therefore, for assembly to occur, MHC class II molecules, foreign proteins, and accessory
molecules must be sorted to appropriate intracellular sites. My laboratory is trying to understand how proteins are sorted
to various antigen-processing compartments as well as to conventional endosomal organelles. Using chimeric marker proteins
and a variety of biochemical and genetic approaches, we are addressing the specificity of protein sorting and the mechanisms
by which sorting signals are deciphered. By using a similar chimeric protein approach to target endogenous proteins to distinct
compartments, we hope to address the role of processing events in each compartment in the generation of MHC class II ligands. 相似文献
63.
Marks GB Ng K Zhou J Toelle BG Xuan W Belousova EG Britton WJ 《The Journal of allergy and clinical immunology》2003,111(3):541-549
BACKGROUND: There are conflicting reports on the effect of BCG vaccination on the subsequent development of atopy and asthma. There are no data on the effects of neonatal BCG vaccination on cytokine responses of lymphocytes that are exposed in vitro to allergens. OBJECTIVES: We sought to test the hypothesis that neonatal BCG vaccination or, alternatively, evidence of an immunologic memory of this vaccination is associated with a reduced prevalence of allergic sensitization, asthma, eczema, and hay fever during childhood. METHODS: An historical cohort study was conducted among 7- to 14-year-old children who were born in 2 districts in Sydney, Australia, and whose mothers were born in southeast Asia. One district had routinely administered BCG vaccination to infants born to overseas-born mothers and the other had not. Eligible subjects were identified from birth registers. Consenting subjects completed questionnaires, performed spirometric and airway hyperresponsiveness testing, and had allergen skin prick testing and tuberculin skin testing. Blood was collected to measure total serum IgE levels and for in vitro lymphocyte culture in the presence of an extract of house dust mite, the dominant allergen in this region, and purified protein derivative of Mycobacterium tuberculosis (tuberculin). IL-4, IL-5, IL-10, and IFN-gamma were measured in the culture supernatant. RESULTS: The cohort included 309 BCG-vaccinated subjects and 442 non-BCG-vaccinated subjects. BCG-vaccinated subjects did not have a lower rate of allergic sensitization than nonvaccinated subjects. However, among the subgroup of subjects with a family history of rhinitis or eczema, BCG vaccination was associated with a lower prevalence of current asthma (defined as recent wheezing plus airway hyperresponsiveness; relative risk, 0.46; 95% CI, 0.22-0.95). BCG vaccination was also associated with lower levels of allergen-stimulated IL-10 production in vitro. Among the BCG-vaccinated subjects, the 44 (14.3%) who had tuberculin skin test reaction sizes of 5 mm or greater and the 31 (18.3%) who demonstrated an in vitro IFN-gamma response to purified protein derivative of M tuberculosis did not have lower rates of allergic sensitization and, overall, did not have a lower prevalence of allergic disease than tuberculin skin test or IFN-gamma nonreactors. CONCLUSION: We conclude that neonatal BCG vaccination has an effect on T-cell allergen responsiveness 7 to 14 years after vaccination and that among a subgroup of subjects with an inherited predisposition to allergic disease, this is associated with clinically relevant beneficial effects. The findings of this study encourage the view that external influences on the immune system in the neonatal period have consequences that extend into later childhood and influence the expression of asthma. Genetic factors are likely to modify the effect of those external factors. 相似文献
64.
65.
Role of antibody to S100 protein in diagnostic pathology 总被引:1,自引:0,他引:1
66.
67.
Starr PA Rau GM Davis V Marks WJ Ostrem JL Simmons D Lindsey N Turner RS 《Journal of neurophysiology》2005,93(6):3165-3176
Dystonia is a movement disorder defined by sustained muscle contractions, causing twisting and repetitive movements and abnormal postures. To understand the abnormalities in pallidal discharge in dystonia, we have analyzed the spontaneous activity of 453 neurons sampled from the internal or external pallidum (GPi or GPe) of 22 patients with dystonia, 140 neurons from 11 patients with Parkinson's disease (PD), and 157 neurons from two normal non-human primates (NHPs; Macacca mulatta). All recordings were performed without systemic sedation. Mean GPi discharge rate in dystonia was 55.3 +/- 1.3 (SE) Hz. This was significantly lower than in the normal NHPs (82.5 +/-2.5 Hz) and lower than in PD patients (95.2 +/- 2.3 Hz). Mean GPe discharge rate in dystonia (54.0 +/- 1.9 Hz) was lower than in the normal NHPs (69.7 +/- 3.3 Hz) and was indistinguishable from that in PD patients (56.6 +/- 3.5 Hz). Mean GPi discharge rate was inversely correlated with dystonia severity. GPi showed increased oscillatory activity in the 2- to 10-Hz range and increased bursting activity in both dystonia and PD as compared with the normal NHPs. Because the abnormalities in discharge patterns were similar in dystonia compared with PD, we suggest that bursting and oscillatory activity superimposed on a high background discharge rate are associated with parkinsonism, whereas similar bursting and oscillations superimposed on a lower discharge rate are associated with dystonia. Our findings are most consistent with a model of dystonia pathophysiology in which the two striatal cell populations contributing to the direct and indirect intrinsic pathways of the basal ganglia both have increased spontaneous activity. 相似文献
68.
Characterization of idiotopes on MOPC 315 IgA using monoclonal antiidiotypic antibodies 总被引:1,自引:0,他引:1
Terresa Nusair Reuben Baumal Robert Rosenstein Trond Jørgensen Alexander Marks 《Molecular immunology》1983,20(5):537-547
The isologous antiidiotypic response in BALB/c mice to immunization with the DNP-binding IgA myeloma protein, MOPC 315, alters the expression of the anti-DNP antibody repertoire and confers immunity against MOPC 315 myeloma tumors. In order to characterize the idiotopes on MOPC 315 IgA which elicit this response we have isolated four monoclonal antiidiotypic antibodies (AIA), D10 (IgG2a), A2(IgG1), G3 (IgG2b) and F1 (IgG2a), produced by splenocytes of BALB/c mice immunized with MOPC 315 IgA in three independent fusion experiments. These AIA react with MOPC 315 IgA. reassociated H315 L315 and F315V but not with free H315, L315, V315H or V3152. In addition the AIA do not react with the closely related DNP-binding IgA myeloma protein, MOPC 460, suggesting that they are directed against private idiotopes on MOPC 315 IgA. These idiotopes can be divided into two groups. Group I, defined by D10, A2 and G3 consists of two overlapping idiotopes, one of which is related to the hapten-binding site. The two idiotopes are formed by an interaction of amino acids in H315 and L315. Group II defined by F1 consists of one idiotope which is related to the hapten-binding site. This idiotope is comprised of an aminoacid sequence on H315 which requires an interaction with either L315 or L460 for expression. A2 and G3 react identically with the same idiotope but were derived from two independent fusion experiments. This indicates an identity of AIA clonotypes among individual mice and suggests that the isologous AIA response to MOPC 315 IgA is restricted. 相似文献
69.
Cytotoxicity of tumor necrosis factor-alpha for human umbilical vein endothelial cells 总被引:10,自引:0,他引:10
L Schuger J Varani R M Marks S L Kunkel K J Johnson P A Ward 《Laboratory investigation; a journal of technical methods and pathology》1989,61(1):62-68
Human umbilical vein endothelial cells were examined for sensitivity to killing by human recombinant tumor necrosis factor-alpha (TNF-alpha). Treatment of the cells with concentrations of TNF-alpha up to 50 ng/ml for 18 hours did not produce evidence of cytotoxicity. However, a marked cytotoxic effect was found when TNF-alpha pretreated cells were incubated in Hanks' balanced salt solution for a further 4 hours. Exposure of the cells to heat-inactivated or antibody-neutralized TNF-alpha did not result in cytotoxicity. Human recombinant interleukin-1 also lysed endothelial cells under the same conditions, whereas human recombinant macrophage-colony stimulating factor did not. Inclusion of superoxide dismutase, catalase, or soybean trypsin inhibitor in the culture medium during the time of endothelial cell exposure to TNF-alpha had no protective effects. Likewise, allopurinol (a xanthine oxidase inhibitor) and nordihydro-guaiaretic acid (a lipoxygenase inhibitor) were not protective under the same conditions. In contrast, the ferric iron chelator deferoxamine mesylate and three different cyclooxygenase inhibitors provided significant protection against TNF-alpha induced cytotoxicity. When human dermal fibroblasts and human squamous epithelial cells were used in place of the umbilical vein endothelial cells, these cells were resistant to TNF-alpha mediated killing. These findings demonstrate that under the experimental conditions employed, TNF-alpha is cytotoxic for human umbilical vein endothelial cells. This may have implications in a number of in vivo situations in which TNF-alpha is thought to play a role. 相似文献
70.
Melanosomes are specialized intracellular compartments within melanocytes and retinal pigment epithelial cells that function
in the synthesis, storage, and secretion of melanins, which are the major pigments made by mammals. The mechanisms that regulate
the formation of melanosomes, and the pathways by which constituent proteins are targeted to them, are related to those involved
in the biogenesis of major histocompatibility complex (MHC) class II antigen-processing compartments. Consequently, diseases
that affect pigmentation may also affect antigen presentation to T cells. Moreover, many of the tissue-specific proteins that
localize to melanosomes and participate in melanin formation double as tumor-associated antigens that are targets for T cells
in patients with melanoma. Our studies on melanosome biogenesis are providing new ways of thinking about antigen-processing
compartments and the mechanisms regulating presentation of tumor-associated antigens. 相似文献