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111.
MP Busch ; EA Operskalski ; JW Mosley ; CE Stevens ; ER Schiff ; SH Kleinman ; H Lee ; M Lee ; M Harris 《Transfusion》1994,34(10):858-864
BACKGROUND: The long-term course of human immunodeficiency virus type 1 (HIV-1)-related disease among seropositive blood donors has not been described. The enrollment and epidemiologic background of HIV-1- infected donors in the Transfusion Safety Study and their immunologic and clinical progression are described. STUDY DESIGN AND METHODS: Through the testing of approximately 200,000 sera from donations made in late 1984 and early 1985, 146 anti-HIV-1-positive donors and 151 uninfected matched donors were enrolled. These two cohorts were followed with 6-month interval histories and laboratory testing. RESULTS: Seropositive donors detected before the institution of routine anti-HIV-1 screening disproportionately were first-time donors and men with exclusively male sexual contacts. The actuarial probability of a person's developing AIDS within 7 years after donation was 40 percent; the probability of a person's dying of AIDS was 28 percent. AIDS developed more often when the donor was p24 antigen-positive at donation. Over a 3-year period, significant decreases occurred in CD4+, CD2+CD26+, CD4+CD29+, and CD20+CD21+ counts, but not in CD8+ subsets, CD20+, or CD14+. CONCLUSION: The high proportions of first-time donations and exclusively homosexual men among seropositive donors suggest that test-seeking may have contributed to the high HIV-1 prevalence in the repository. Implementation of alternative test sites when routine donor screening began in 1985 may have averted many high- risk donations. The disease course in HIV-1-infected donors had the same wide spectrum of immunologic and clinical manifestations as were reported for other cohorts. 相似文献
112.
Pashley CH Fairs A Morley JP Tailor S Agbetile J Bafadhel M Brightling CE Wardlaw AJ 《Medical mycology》2012,50(4):433-438
Colonization of the airways by filamentous fungi can occur in asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. A recent study found IgE sensitization to Aspergillus fumigatus to be associated with reduced lung function. Significantly higher rates of A. fumigatus were detected in sputum from asthmatics sensitized to this fungus compared to non-sensitized asthmatics. The rate of positive cultures was far higher than equivalent historical samples analysed by the local clinical laboratory following protocols recommended by the UK Health Protection Agency (HPA). This study compares the HPA procedure with our sputum processing method, whereby sputum plugs are separated from saliva and aliquots of approximately 150 mg are inoculated directly onto potato dextrose agar. A total of 55 sputum samples from 41 patients with COPD were analyzed, comparing fungal recovery of five dilutions of sputa on two media. Isolation of A. fumigatus in culture was significantly higher using the research approach compared to the HPA standard method for mycological investigations (P < 0.001). There was also a significant difference in the recovery rate of A. fumigatus (P < 0.05) between media. This highlights the need for a standardized approach to fungal detection which is more sensitive than the method recommended by the HPA. 相似文献
113.
114.
I D Pavord S S Birring M Berry R H Green C E Brightling A J Wardlaw 《The European respiratory journal》2006,27(5):884-888
Refractory or difficult-to-control asthma is associated with some clinical and pathological features normally associated with chronic obstructive pulmonary disease (COPD), raising the possibility that there are similarities in their pathogenesis. It is suggested that the coexistence of two or more inflammatory stimuli to the airway (multiple hits) is a key factor leading to the development of more severe airway disease. Airway inflammation in response to chronic inflammatory conditions elsewhere may be a particularly important additional inflammatory stimulus. The "multiple hit" hypothesis for the origins of severe airway disease has important implications for treatment and prevention, since identification and removal of additional inflammatory stimuli may delay progression of the underlying airway disease. 相似文献
115.
本研究在于确定胃酸抑制剂是否会增加选择性手术患者术后发生肺炎的风险。
此项人群前瞻性队列研究于1992年4月1日-2008年3月31日在加拿大开展。年龄大于65岁已确定进行选择性手术的患者入组。将本年度在手术前服用过两种或以上胃酸抑制剂的患者以及术前90天内服用过至少一种胃酸抑制剂的患者入试验组, 相似文献
116.
K Mutalithas C Guillen C Day C E Brightling I D Pavord A J Wardlaw 《Clinical and experimental immunology》2010,161(1):34-40
Mast cell‐derived prostaglandin D2 (PGD2) is the major prostanoid found within the airway of asthmatics immediately following allergen challenge. PGD2 has been shown to have chemokinetic effects on eosinophils and T helper type 2 (Th2) cells in vitro. This occurs through the interaction of PGD2 with the G‐protein‐coupled chemokine receptor homologous molecule expressed on Th2 lymphocytes (CRTH2). The expression of CRTH2 has been shown to be highly selective for Th2 cells. Using flow cytometry we have studied the expression of CRTH2 on T cells in blood and bronchoalveolar lavage fluid in asthmatics and normal subjects. CRTH2 expression was confined to a small percentage of blood T cells in asthmatics (1·8% ± 0·2) and normal (1·6% ± 0·2) subjects. CRTH2 was enriched significantly on interleukin (IL)‐4+/IL‐13+ T cells compared to interferon (IFN)‐γ+ T cells (P < 0·001). There was a small population of CRTH2+ T cells in the bronchoalveolar lavage (BAL) of asthmatics (2·3% ± 0·6) and normal subjects (0·3% ± 0·1), and there was a significant difference between the two groups (P < 0·05). There were similar amounts of PGD2 in the BAL of asthma and normal subjects. Within paired blood–BAL samples from the same subject there was no increase in CRTH2+ T cells in the BAL compared to blood in asthmatics. Enrichment of CRTH2 on IL‐4+ and IL‐13+ T cells compared to IFN‐γ+ T cells was also seen in BAL from asthmatics (P < 0·001). CRTH2 is expressed preferentially by IL‐4+/IL‐13+ T cells compared to IFN‐γ+ T cells. However, given their small numbers they are unlikely to have a significant involvement in the pathogenesis of asthma. CRTH2 antagonism may not diminish T cell accumulation in the asthmatic lung. 相似文献
117.
Duffy SM Cruse G Cockerill SL Brightling CE Bradding P 《European journal of immunology》2008,38(9):2548-2556
Human lung mast cells (HLMC) express the Ca(2+)-activated K(+) channel K(Ca)3.1, which plays a crucial role in their migration to a variety of diverse chemotactic stimuli. K(Ca)3.1 activation is attenuated by the beta(2)-adrenoceptor and the adenosine A(2A) receptor through a G(s)-coupled mechanism independent of cyclic AMP. Prostaglandin E(2) promotes degranulation and migration of mouse bone marrow-derived mast cells through the G(i)-coupled EP(3) prostanoid receptor, and induces LTC(4) and cytokine secretion from human cord blood-derived mast cells. However, PGE(2) binding to the G(s)-coupled EP(2) receptor on HLMC inhibits their degranulation. We show that EP(2) receptor engagement closes K(Ca)3.1 in HLMC. The EP(2) receptor-specific agonist butaprost was more potent than PGE(2) in this respect, and the effects of both agonists were reversed by the EP(2) receptor antagonist AH6809. Butaprost markedly inhibited HLMC migration induced by chemokine-rich airway smooth muscle-conditioned media. Interestingly, PGE(2) alone was chemotactic for HLMC at high concentrations (1 microM), but was a more potent chemoattractant for HLMC following EP(2) receptor blockade. Therefore, the G(s)-coupled EP(2) receptor closes K(Ca)3.1 in HLMC and attenuates both chemokine- and PGE(2)-dependent HLMC migration. EP(2) receptor agonists with K(Ca)3.1 modulating function may be useful for the treatment of mast cell-mediated disease. 相似文献
118.
Saha S Mistry V Siva R Parker D May R Bradding P Pavord ID Brightling CE 《Allergy》2008,63(9):1239-1243
Background: The Th2 cytokine interleukin-13 (IL-13) has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). We sought to examine IL-13 expression in COPD subjects in induced sputum and bronchus specimens. We hypothesized that inflammatory cells expressing IL-13 localize to the airway smooth muscle bundle and bronchial glands.
Methods: Interleukin-13 was measured in sputum samples from subjects with COPD ( n = 34) across a range of severity (Global initiative for chronic Obstructive Lung Disease 2–4) and controls ( n = 14) using ELISA. IL-13+ cells and inflammatory cells were enumerated within surgically resected proximal airway using immunohistochemical techniques from subjects with COPD ( n = 10), smoking ( n = 10) and nonsmoking controls ( n = 8).
Results: Sputum IL-13 was measurable in only 6/34 subjects with COPD and was not found in the smoking or nonsmoking control subjects. In subjects with COPD and controls there was a paucity of IL-13+ cells. The distribution of inflammatory cells within different airway compartments was similar in COPD and controls except for an increase in CD3+ lymphocytes within bronchial glands in COPD ( P = 0.04).
Conclusions: Our findings do not support a role for IL-13 in COPD. However, the tissue localization of inflammatory cells to airway compartments, particularly the increase of T cells in glands in COPD may be important in disease. 相似文献
Methods: Interleukin-13 was measured in sputum samples from subjects with COPD ( n = 34) across a range of severity (Global initiative for chronic Obstructive Lung Disease 2–4) and controls ( n = 14) using ELISA. IL-13+ cells and inflammatory cells were enumerated within surgically resected proximal airway using immunohistochemical techniques from subjects with COPD ( n = 10), smoking ( n = 10) and nonsmoking controls ( n = 8).
Results: Sputum IL-13 was measurable in only 6/34 subjects with COPD and was not found in the smoking or nonsmoking control subjects. In subjects with COPD and controls there was a paucity of IL-13+ cells. The distribution of inflammatory cells within different airway compartments was similar in COPD and controls except for an increase in CD3
Conclusions: Our findings do not support a role for IL-13 in COPD. However, the tissue localization of inflammatory cells to airway compartments, particularly the increase of T cells in glands in COPD may be important in disease. 相似文献
119.
Derwall M Francis RC Kida K Bougaki M Crimi E Adrie C Zapol WM Ichinose F 《Critical care (London, England)》2011,15(1):R51
Introduction
Although inhalation of 80 parts per million (ppm) of hydrogen sulfide (H2S) reduces metabolism in mice, doses higher than 200 ppm of H2S were required to depress metabolism in rats. We therefore hypothesized that higher concentrations of H2S are required to reduce metabolism in larger mammals and humans. To avoid the potential pulmonary toxicity of H2S inhalation at high concentrations, we investigated whether administering H2S via ventilation of an extracorporeal membrane lung (ECML) would provide means to manipulate the metabolic rate in sheep. 相似文献120.
Pramana IA Latzin P Schlapbach LJ Hafen G Kuehni CE Nelle M Riedel T Frey U 《European journal of medical research》2011,16(5):223-230