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121.
The cytokines interleukin-3 (IL-3); IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) are known to contribute to the proliferation and differentiation of eosinophil progenitors. Recently, it was determined that the cellular receptors for these three cytokines share a common beta-chain while having unique alpha-chains. Thus, there is considerable interest in how these cytokines and their receptors interact in promoting production of eosinophils. We have established a cell line (AML14) from a patient with acute myelogenous leukemia that will consistently exhibit eosinophilic differentiation in suspension in response to IL-3, IL-5, and GM-CSF. Proliferation with only modest differentiative effects was observed in response to a single cytokine. Combinations of two cytokines gave variable results, with GM-CSF + IL-3 and IL-3 + IL-5 causing more proliferation than a single cytokine but little more differentiation. The combination of GM-CSF + IL-5 caused marked enhancement of eosinophilic differentiation with only modest augmentation of proliferation. The combination of all three cytokines was most effective in stimulating both proliferation and eosinophilic differentiation (up to 70% of cells) of AML14 cells. Specific binding of GM-CSF and IL-5 to AML14 cells can be conveniently studied by flow cytometric methods, and cross-competition of these two cytokines for their respective receptors was demonstrated. IL-3 was shown to partially compete for IL-5 binding on AML14 cells. Although specific IL- 3 binding could not be demonstrated by flow cytometry, mRNA for the alpha-chains of the IL-3, IL-5, and GM-CSF receptors and the beta-chain common to all three receptors was detected in AML14 cells. The AML14 cell line may be a useful model for the study of cooperative interactions of IL-3, IL-5, GM-CSF, and their respective receptors in the promotion of eosinophil progenitor growth and differentiation. 相似文献
122.
Neutrophil-mediated protection of cultured human vascular endothelial cells from damage by growing Candida albicans hyphae 总被引:10,自引:0,他引:10
Interactions were studied between human neutrophils and cultured human umbilical vein endothelial cells invaded by Candida albicans. In the absence of neutrophils, progressive Candida germination and hyphal growth extensively damaged endothelial cell monolayers over a period of 4 to 6 hours, as determined both by morphological changes and release of 51Cr from radiolabeled endothelial cells. Monolayers were completely destroyed and replaced by hyphae after 18 hours of incubation. In contrast, when added 2 hours after the monolayers had been infected with Candida, neutrophils selectively migrated toward and attached to hyphae at points of hyphal penetration into individual endothelial cells (observed by time-lapse video-microscopy). Attached neutrophils spread over hyphal surfaces both within and beneath the endothelial cells; neutrophil recruitment to initial sites of leukocyte-Candida- endothelial cell interactions continued throughout the first 60 minutes of observation. Neutrophil spreading and stasis were observed only along Candida hyphae and at sites of Candida-endothelial cell interactions. These events resulted in 58.0% killing of Candida at 2 hours and subsequent clearance of Candida from endothelial cell monolayers, as determined by microcolony counts and morphological observation. On introduction of additional neutrophils to yield higher ratios of neutrophils to endothelial cells (10 neutrophils:1 endothelial cell), neutrophil migration toward hyphal elements continued. Despite retraction or displacement of occasional endothelial cells by invading Candida and neutrophils, most endothelial cells remained intact, viable, and motile as verified both by morphological observations and measurement of 51Cr release from radiolabeled monolayers. From these studies, we conclude that neutrophils are capable of killing Candida hyphae selectively within human vascular endothelial cell monolayers and may have protective rather than detrimental effects on endothelial cell integrity. 相似文献
123.
Evaluation of E-rosetting human lymphocytes with OKT11 and other monoclonal antibodies 总被引:2,自引:0,他引:2
Ip SH; Rittershaus CW; Struzziero CC; Hoxie JA; Hoffman RA; Healey KW; Lifter J 《Blood》1982,60(3):795-799
Monoclonal antibody OKT11 was found to compete with sheep red blood cells for binding sites on human lymphocytes. Preincubation of lymphocytes with OKT11 eliminated E-rosette formation. In a study of 142 peripheral blood samples ranging from 1% to over 90% E-rosette- positive cells, comparison to the percent OKT11-positive cells yielded a correlation coefficient of 0.93. In normal donors, subsets of OKT11+ cells were identified using two-color immunofluorescent staining methods with OKT3, OKT4, and OKT8. On the average, approximately 13% of OKT11+ lymphocytes were OKT3- and 13% of OKT11+ lymphocytes were OKT4- and OKT8-. Based on our double antibody fluorescence intensity data, low antigen density OKT11+ lymphocytes were OKT3-. OKT4+ and OKT8+ lymphocytes in normal peripheral lymphocytes have similar OKT11 antigen density. 相似文献
124.
AC Justice KA McGinnis M Skanderson CC Chang CL Gibert MB Goetz D Rimland MC Rodriguez‐Barradas KK Oursler ST Brown RS Braithwaite M May KE Covinsky MS Roberts SL Fultz KJ Bryant for the VACS Project Team 《HIV medicine》2010,11(2):143-151
Background
As those with HIV infection live longer, ‘non‐AIDS’ condition associated with immunodeficiency and chronic inflammation are more common. We ask whether ‘non‐HIV’ biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART).Methods
Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV‐infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS‐defining conditions); ‘non‐HIV’ biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data.Results
Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle‐aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and ‘non‐HIV’ markers were associated with each other (P<0.0001) and discriminated mortality (C statistics 0.68–0.73); when combined, discrimination improved (P<0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30‐day C statistic 0.86, 95% confidence interval (CI) 0.80–0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72–0.74). Results were robust to adjustment for missing data.Conclusions
When added to HIV biomarkers, ‘non‐HIV’ biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research. 相似文献125.
Roehr CC Gröbe S Rüdiger M Hummler H Nelle M Proquitté H Hammer H Schmalisch G 《European journal of medical research》2010,15(11):493-503
Background
Surveys from the USA, Australia and Spain have shown significant inter-institutional variation in delivery room (DR) management of very low birth weight infants (VLBWI, < 1500 g) at birth, despite regularly updated international guidelines.Objective
To investigate protocols for DR management of VLBWI in Germany, Austria and Switzerland and to compare these with the 2005 ILCOR guidelines.Methods
DR management protocols were surveyed in a prospective, questionnaire-based survey in 2008. Results were compared between countries and between academic and non-academic units. Protocols were compared to the 2005 ILCOR guidelines.Results
In total, 190/249 units (76%) replied. Protocols for DR management existed in 94% of units. Statistically significant differences between countries were found regarding provision of 24 hr in house neonatal service; presence of a designated resuscitation area; devices for respiratory support; use of pressure-controlled manual ventilation devices; volume control by respirator; and dosage of Surfactant. There were no statistically significant differences regarding application and monitoring of supplementary oxygen, or targeted saturation levels, or for the use of sustained inflations. Comparison of academic and non-academic hospitals showed no significant differences, apart from the targeted saturation levels (SpO2) at 10 min. of life. Comparison with ILCOR guidelines showed good adherence to the 2005 recommendations.Summary
Delivery room management in German, Austrian and Swiss neonatal units was commonly based on written protocols. Only minor differences were found regarding the DR setup, devices used and the targeted ranges for SpO2 and FiO2. DR management was in good accordance with 2005 ILCOR guidelines, some units already incorporated evidence beyond the ILCOR statement into their routine practice. 相似文献126.
Wobbe Bouma Theo J Klinkenberg Iwan CC van der Horst Inez J Wijdh-den Hamer Michiel E Erasmus Marc Bijl Albert JH Suurmeijer Felix Zijlstra Massimo A Mariani 《Journal of cardiothoracic surgery》2010,5(1):13
Libman-Sacks endocarditis of the mitral valve was first described by Libman and Sacks in 1924. Currently, the sterile verrucous
vegetative lesions seen in Libman-Sacks endocarditis are regarded as a cardiac manifestation of both systemic lupus erythematosus
(SLE) and the antiphospholipid syndrome (APS). Although typically mild and asymptomatic, complications of Libman-Sacks endocarditis
may include superimposed bacterial endocarditis, thromboembolic events, and severe valvular regurgitation and/or stenosis
requiring surgery. In this study we report two cases of mitral valve repair and two cases of mitral valve replacement for
mitral regurgitation (MR) caused by Libman-Sacks endocarditis. In addition, we provide a systematic review of the English
literature on mitral valve surgery for MR caused by Libman-Sacks endocarditis. This report shows that mitral valve repair
is feasible and effective in young patients with relatively stable SLE and/or APS and only localized mitral valve abnormalities
caused by Libman-Sacks endocarditis. Both clinical and echocardiographic follow-up after repair show excellent mid- and long-term
results. 相似文献
127.
Y Wang WC Huang CY Wang CC Tsai CL Chen YT Chang JI Kai CF Lin 《British journal of pharmacology》2009,157(6):1004-1013
Background and purpose:
Excessive inflammation and apoptosis are pathological features of endotoxaemic acute renal failure. Activation of glycogen synthase kinase-3 (GSK-3) is involved in inflammation and apoptosis. We investigated the effects of inhibiting GSK-3 on lipopolysaccharide (LPS)-induced acute renal failure, nuclear factor-κB (NF-κB), inflammation and apoptosis.Experimental approach:
The effects of inhibiting GSK-3 with inhibitors, including lithium chloride (LiCl) and 6-bromo-indirubin-3′-oxime (BIO), on LPS-treated (15 mg·kg−1) C3H/HeN mice (LiCl, 40 mg·kg−1 and BIO, 2 mg·kg−1) and LPS-treated (1 µg·mL−1) renal epithelial cells (LiCl, 20 mM and BIO, 5 µM) were studied. Mouse survival was monitored and renal function was analysed by histological and serological examination. Cytokine and chemokine production, and cell apoptosis were measured by enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated dUTP–biotin nick-end labelling staining, respectively. Activation of NF-κB and GSK-3 was determined by immunostaining and Western blotting, respectively.Key results:
Mice treated with GSK-3 inhibitors showed decreased mortality, renal tubular dilatation, vacuolization and sloughing, blood urea nitrogen, creatinine and renal cell apoptosis in response to endotoxaemia. Inhibiting GSK-3 reduced LPS-induced tumour necrosis factor-α (TNF-α) and CCL5/RANTES (released upon activation of normal T-cells) in vivo in mice and in vitro in murine kidney cortical collecting duct epithelial M1 cells. Inhibiting GSK-3 did not block TNF-α-induced cytotoxicity in rat kidney proximal tubular epithelial NRK52E or in M1 cells.Conclusions and implications:
These results suggest that GSK-3 inhibition protects against endotoxaemic acute renal failure mainly by down-regulating pro-inflammatory TNF-α and RANTES. 相似文献128.
Background and purpose:
Human pancreatic carcinoma is a highly malignant cancer. Previous studies have shown that the decoy receptor 3 (DcR3) for Fas ligand (FasL) plays significant roles in tumour progression and immune suppression. In the present study, we evaluated the anti-cancer activity of a natural compound, denbinobin (5-hydroxy-3,7-dimethoxy-1,4-phenanthraquinone), through decreasing DcR3 levels in human pancreatic adenocarcinoma cell lines.Experimental approach:
We used immunoprecipitation and ELISA assays to examine DcR3 levels, and used FACS to determine the percentage of cells with a sub-G1 DNA content.Key results:
AsPC-1 and BxPC-3 human pancreatic cancer cells express high levels of DcR3. Denbinobin concentration-dependently decreased DcR3 levels in BxPC-3 cells. MTT and flow cytometry assays indicated that BxPC-3 was FasL-resistant because high concentrations (100 ng·mL−1) of soluble FasL did not inhibit cell growth. However, combinations of denbinobin (3 µmol·L−1) with lower concentrations of soluble FasL (10, 30 and 50 ng·mL−1) or membrane-bound FasL, were synergistic on cell growth inhibition and apoptosis. Exogenous excess DcR3 reversed this synergistic effect. We observed no significant increase in the levels of surface Fas, cleaved forms of caspase-8, -3, -9, Bax, Bid, Bcl-xL, cytochrome c or mitochondrial membrane potentials following denbinobin treatment. However, denbinobin treatment increased the levels of apoptosis-inducing factor.Conclusions and implications:
Denbinobin and FasL trigger a synergistic cytotoxic effect in human pancreatic adenocarcinoma cells. Denbinobin mediated a decrease in levels of DcR3, which played a major role in this synergistic effect, and also increased caspase-independent apoptosis, via apoptosis-inducing factor. 相似文献129.
Objectives
The aim of the study was to elucidate primary drug resistance and transmission of HIV‐1 in acute and recent drug‐naïve seroconverters in Singapore.Methods
Acute and recent HIV‐1 seroconverters were enrolled in the study. The HIV‐1 polymerase (pol) gene was sequenced and used for genotypic drug resistance analysis and phylogenetic analysis. HIV‐1 transmission clusters were inferred from phylogenetic clustering analysis.Results
Of the 60 subjects analysed, 95% were men, and 73.3% were men who have sex with men (MSM). Six HIV‐1 subtypes were identified, including CRF01_AE (46.7%), subtypes B (30%), B′ (15%) and G (1.7%), CRF33_01B (1.7%) and CRF34_01B (5%). Primary genotypic resistance was detected in only one (1.7%) subtype B variant. Thirty‐one patients (51.7%) were phylogenetically clustered, of whom 90% reported having local risk exposure, compared with 59% of the patients who were not phylogenetically clustered [odds ratio (OR) 6.35, 95% confidence interval (CI) 1.65–23.95]. MSM (OR 5.63, 95% CI 1.17–27.15), high viral load (OR 4.28, 95% CI 1.37–13.36) and young age (OR 0.92, 95% CI 0.85–0.99) were independently associated with clustered individuals.Conclusions
In Singapore, HIV‐1 primary resistance is insignificant; individuals with seroconversion account for about half of onward transmission among recently infected seroconverters. MSM, high viral load and young age are factors that facilitate transmission. Early detection of these individuals is of paramount importance for the prevention of HIV‐1 transmission.130.