全文获取类型
收费全文 | 3437篇 |
免费 | 208篇 |
国内免费 | 64篇 |
专业分类
耳鼻咽喉 | 26篇 |
儿科学 | 137篇 |
妇产科学 | 13篇 |
基础医学 | 508篇 |
口腔科学 | 14篇 |
临床医学 | 509篇 |
内科学 | 718篇 |
皮肤病学 | 7篇 |
神经病学 | 12篇 |
特种医学 | 66篇 |
外科学 | 309篇 |
综合类 | 569篇 |
预防医学 | 265篇 |
眼科学 | 8篇 |
药学 | 364篇 |
4篇 | |
中国医学 | 78篇 |
肿瘤学 | 102篇 |
出版年
2024年 | 3篇 |
2023年 | 36篇 |
2022年 | 79篇 |
2021年 | 154篇 |
2020年 | 128篇 |
2019年 | 105篇 |
2018年 | 98篇 |
2017年 | 89篇 |
2016年 | 100篇 |
2015年 | 107篇 |
2014年 | 244篇 |
2013年 | 235篇 |
2012年 | 216篇 |
2011年 | 223篇 |
2010年 | 162篇 |
2009年 | 143篇 |
2008年 | 164篇 |
2007年 | 153篇 |
2006年 | 131篇 |
2005年 | 130篇 |
2004年 | 108篇 |
2003年 | 76篇 |
2002年 | 79篇 |
2001年 | 78篇 |
2000年 | 63篇 |
1999年 | 68篇 |
1998年 | 69篇 |
1997年 | 61篇 |
1996年 | 52篇 |
1995年 | 57篇 |
1994年 | 51篇 |
1993年 | 34篇 |
1992年 | 33篇 |
1991年 | 27篇 |
1990年 | 32篇 |
1989年 | 23篇 |
1988年 | 24篇 |
1987年 | 11篇 |
1986年 | 12篇 |
1985年 | 17篇 |
1984年 | 13篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有3709条查询结果,搜索用时 15 毫秒
991.
U. Pipkorn G. Granerus D. Proud A. Kagey-Sobotka P. S. Norman L. M. Lichtenstein R. M. Naclerio 《Allergy》1987,42(7):496-501
We studied the effect of alpha-fluoromethyl histidine, an irreversible histamine synthesis inhibitor, on the immediate nasal reaction to antigen challenge in a double-blind, placebo controlled, randomized, parallel study using 13 subjects. The patients received either active drug 100 mg twice daily or placebo, for 3 weeks. A nasal allergen challenge was performed before and after at weekly intervals. Symptoms at challenge were assessed and the levels of histamine, TAME-esterase activity and kinins were measured in nasal lavages before and after antigen challenge. Skin tests were also performed at weekly intervals. In addition, the urinary excretion of the main histamine metabolite, telemethylimidazole acetic acid, was measured before and after 3 weeks of treatment. The active treatment induced 60% reduction in histamine levels in the lavage fluids before and after antigen challenge, as well as a reduction in the histamine levels in the lavage fluids before and after antigen challenge, as well as a reduction in the main urinary histamine metabolite. However, no reduction was found in nasal symptoms obtained after antigen challenge. The levels of kinins and TAME-esterase activity were not significantly reduced. 相似文献
992.
Powell TJ Brown DM Hollenbaugh JA Charbonneau T Kemp RA Swain SL Dutton RW 《Clinical immunology (Orlando, Fla.)》2004,113(1):89-100
The activation, localization, phenotypic changes, and function of CFSE-labeled naive influenza-specific CD8(+) and CD4(+) T cells following influenza infection were examined. Response of adoptively transferred CD8(+) T cells was seen earliest in draining lymph node. Highly activated cells were found later in the lung, airways, and spleen, were cytolytic, and expressed IFN-gamma upon restimulation. Similar amounts of division at early time points, but higher numbers of CD8(+) T cells, were detected at 9 and 30 days postinfection after cotransfer of CD4(+) and CD8(+) T cells followed by infection. Transfer of much smaller numbers of CD4(+) and CD8(+) T cells led to more extensive expansion but the same difference in final number between the two cell types. These studies demonstrate how CD8(+) and CD4(+) T cells respond to influenza at early time points postinfection and the differential kinetics of antigen-specific CD4(+) and CD8(+) T cells. 相似文献
993.
Ji-Yeon Park Joo-Hee Choi Sang-Nam Lee Hyung-Ju Cho Ji-Suk Ahn Yong-Bum Kim Do-Yong Park Sang Chul Park Soo-In Kim Min-Jung Kang Ah-Ra Jang Jae-Hun Ahn Tae-Sung Lee Dong-Yeon Kim Sung Jae Shin Joo-Heon Yoon Jong-Hwan Park 《The Journal of allergy and clinical immunology》2021,147(5):1720-1731
- Download : Download high-res image (120KB)
- Download : Download full-size image
994.
高氧致早产鼠BALF及肺组织中MDA、SOD的变化 总被引:1,自引:0,他引:1
目的观察丙二醛(MDA)、超氧化物歧化酶(SOD)在高氧致(CLD)早产鼠支气管肺泡灌洗液(BALF)及肺组织中的变化.方法用高浓度氧致早产鼠CLD为研究对象,应用生化方法同步检测肺组织和BALF中MDA含量及SOD的活性.结果实验组肺组织中SOD的活性呈升高趋势,但与对照组比较,肺组织和BALF中SOD的活性均无差异(P>0.05、P>0.05),实验组肺组织和BALF中MDA的水平呈同相变化,自吸入高氧的第3d开始升高,(P<0.05),7d达高峰并持续至14d(P<0.01),21d时虽有下降,但仍高于对照组(P<0.05).结论 SOD、MDA的动态变化,可间接反应肺部疾病的变化,对慢性肺疾病的诊断、鉴别诊断、活动性判断及预后均有一定的价值.同时也证实机体的氧化与抗氧化失衡是高氧所致早产儿慢性肺疾病的发病原因之一. 相似文献
995.
P. Clementsen N. Milman E. Struve-Christensen B. Nüchel Petersen M. Pedersen H. Bisgaard H. Permin S. Norn 《Allergy》1991,46(1):45-51
Histamine release induced by Staphylococcus aureus was examined in cells obtained by bronchoalveolar lavage (BAL) in non-atopic individuals. Approximately half of the individuals responded with mediator release to the bacterium, and the release was found to be time- and concentration dependent. No difference was found between the patients who responded and those who did not respond in regard to age, sex, smoker/non-smoker, % recovery of BAL-fluid, total cell count, differential cell counts, histamine content per mast cell, or diagnoses. Also stimulation of the BAL-cells with the calcium-ionophore A23187 resulted in histamine release. S. aureus-induced histamine release from basophils was examined in leukocyte suspensions obtained from the same individuals, and in all experiments release was found. The dose-response curves were similar to those obtained with BAL cells. The bacteria-induced mediator release from superficially lying cells in the airways epithelium might be of importance for the precipitation or exacerbation of bronchial asthma in respiratory tract infections. 相似文献
996.
Erin EM Leaker BR Zacharasiewicz AS Higgins LA Williams TJ Boyce MJ de Boer P Durham SR Barnes PJ Hansel TT 《Allergy》2005,60(12):1524-1529
BACKGROUND: Nasal lavage is a noninvasive method of obtaining inflammatory exudates following nasal allergen challenge (NAC), and permits cells and released mediators to be evaluated. Objective: To determine the effects of a single dose of topical steroid on eosinophils and levels of chemokines and cytokines in nasal lavage fluid following NAC in patients with allergic rhinitis. METHODS: Patients with grass pollen seasonal allergic rhinitis (n = 32) out of the allergy season received either nasal budesonide (100 microg per nostril) or matched placebo before allergen challenge in a double blind two-way crossover design. A semi-automated mixed bead array system was employed to measure multiple chemokines and cytokines in small volumes (50 microl) of nasal lavage supernatants. RESULTS: Following NAC there was a rapid onset of nasal symptoms together with nasal eosinophilia, and the appearance of IL-5 and IL-13 in lavages between 4 and 8 h. Elevated levels of eotaxin, RANTES, IL-8 and MCP-1 were also detected following allergen challenge. A single dose of nasal budesonide caused a decrease in symptoms (P < 0.05) and nasal eosinophils (P < 0.05) with selective abrogation of IL-5 and IL-13 responses (P < 0.05), but a lack of effect on levels of eotaxin, RANTES, IL-8 and MCP-1. CONCLUSION: This study suggests that a single dose of nasal steroid has the capacity to selectively abolish IL-5 and IL-13 responses following NAC. This model should be convenient for testing novel anti-inflammatory and immunoregulatory agents intended for the treatment of allergic rhinitis. 相似文献
997.
Gabriele Di Lorenzo MD Pasquale Mansueto MD Marcello Melluso MD Giuseppina Candore PhD Alfredo Colombo MD Maria Esposito Pellitteri MD Agata Drago MD Marcella Potestio SciD Calogero Caruso MD 《The Journal of allergy and clinical immunology》1997,100(6):832-837
Background: In allergic rhinitis, mast cells, activated by cross-linking of allergen to mast cell–bound specific IgE, release both vasoactive mediators related to the early nasal symptoms and chemotactic mediators that attract inflammatory cells, such as eosinophils, related to the late-phase response. Objective: We have analyzed, during and out of pollen season, in blood and nasal fluid from patients allergic to grass pollen, histamine and tryptase to monitor the early phase markers and eosinophil and eosinophil cationic protein (ECP) to monitor the late phase. Methods: Twenty patients were enrolled in the study. As a control, we studied 10 nonatopic subjects. Mediators and eosinophils were assessed in blood and nasal fluid. Histamine was tested only in nasal fluid. Results: During pollen season, tryptase but not histamine increased in nasal fluids from patients (2.96 vs 0.22 U/ml, p = 0.001) and correlated with symptom scores (rs = 0.63, p = 0.003). Tryptase was not detected in serum. Eosinophils increased in nasal cytology (17.0% vs 2.0%, p = 0.001) and in the blood (26.5 vs 12.7 × 106 L, p = 0.001) from patients, but they did not correlate with symptom scores. ECP increased only in the nasal lavage (16.33 vs 1.30 ng/ml, p = 0.001) and correlated with symptom scores (rs = 0.53, p = 0.016). Conclusions: Both ECP and tryptase increase in nasal secretion in natural disease. Therefore the measurement of tryptase and ECP levels in nasal fluid might be a useful clinical test for monitoring disease activity and the effects of therapeutic agents. (J Allergy Clin Immunol 1997;100:832-7.) 相似文献
998.
H J MILBURN L W POULTER A DILMEC G M COCHRANE D M KEMENY 《Clinical and experimental immunology》1997,108(1):105-113
In this study, we have investigated the balance between Th1- and Th2-like activity in the lungs in sarcoidosis and have determined the effect of corticosteroid treatment on this. Twenty-one patients with acute untreated sarcoidosis were investigated by bronchoalveolar lavage (BAL) and compared with 11 normal volunteers. Sixteen of the sarcoid patients required corticosteroid therapy and seven of these were reinvestigated after 2–3 months'' treatment. In order to assess Th1- and Th2-like activity in the lungs, IgG subclasses and IgE were measured in BAL fluid and serum, and IL-2, IL-4 and interferon-gamma (IFN-γ) in BAL. In patients with untreated sarcoidosis, albumin-corrected BAL/serum ratios for IgG4 and IgE were significantly reduced (IgG4, 1.04±0.18 (mean±s.e.m.); IgE 9.58±3.11) compared with those in normal controls (IgG4 5.3±0.72, P<0.001; IgE 67.7±28.9, P<0.01). Estimates of actual levels of immunoglobulins produced in the lungs were also made and showed extremely high levels of total IgG in sarcoid patients (39.56±8.2 mg/l ) compared with controls (1.17±0.5 mg/l, P<0.001). Although there was no difference between the groups in amount of IgG4 locally produced, the proportion of total IgG which was IgG4 was greatly reduced in those with sarcoidosis (1.6±0.4% compared with 38.5±3.2%; P<0.001). Lavage levels of IL-4 were also reduced in sarcoid patients (IL-4 2.103±0.21 pg/ml) compared with those in normals (IL-4 6.8±1.05; P<0.001). Levels of IL-2 were lower (7.63±0.51 pg/ml compared with 9.4±0.95 pg/ml), but this difference was not significant. IFN-γ, however, could not be detected above 0.4 pg/ml in any of the normal lavage fluid, but was detectable in 12/21 patients with sarcoidosis (χ2=7.74; P<0.001). These changes reverted towards normal on treatment with oral corticosteroids. The mean albumin-corrected BAL/serum ratio for IgG4 before treatment was 0.88±0.33 compared with 5.5±2.1 (P<0.05) on treatment, and for IgE before treatment 9.52±2.15 compared with 50.8±17.9 (P<0.05) on treatment. Total IgG produced in the lung fell from 26.16±7.9 to 6.12±2.4 mg/l (P<0.001) on treatment, and the proportion of IgG4 locally produced rose from 2.3±0.8% to 23.9±6.1% (P<0.01). The mean level of IL-4 in lavage before treatment was 2.53±0.34 pg/ml compared with 4.7±0.34 (P<0.001) on treatment. Levels of IL-2 also rose significantly on treatment from 8.74±0.95 pg/ml before to 14.44±1.38 pg/ml (P<0.001) on treatment. Levels of IFN-γ fell from 1.65±0.43 pg/ml before treatment to undetectable levels in all patients (P<0.001) on treatment. These results demonstrate an imbalance between Th1- and Th2-like activity in the lungs in sarcoidosis, with suppression of Th2 and increase in Th1. Corticosteroid therapy restores the normal balance between Th1 and Th2 cytokines and immunoglobulins in the lungs, suggesting an effect on local immune regulation. 相似文献
999.
HIV-1 proviral DNA copy number in peripheral blood leucocytes and bronchoalveolar lavage cells of AIDS patients.
下载免费PDF全文
![点击此处可从《Clinical and experimental immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
J R Clarke A J Gates R J Coker J A Douglass J D Williamson D M Mitchell 《Clinical and experimental immunology》1994,96(2):182-186
In this study we have determined by polymerase chain reaction (PCR) the quantity of HIV-1 proviral DNA in cells obtained by bronchoalveolar lavage (BAL) from the lung of HIV-1+ individuals. This has been compared quantitatively with the proviral DNA in peripheral blood leucocytes (PBL) obtained simultaneously from the same patients. The mean HIV DNA copy number per 10(6) cells was 391 for PBL, with a range of 1-9000, and 2971 for BAL cells, with a range of < 1-70,000. The quantity of HIV DNA detected in BAL cells was higher than that detected in the corresponding PBL samples in 44 out of 78 (56%) individuals, whilst more HIV DNA was detected in the PBL compared with BAL cells in 14 out of 78 (18%) patients. In both BAL and PBL higher levels of HIV DNA were detected in the adherent (monocyte/macrophage) enriched cell populations compared with other non-adherent cells (leucocytes). A direct relationship between HIV DNA copy number and ability to recover infectious HIV progeny in vitro by co-cultivation with cord blood leucocytes was found for both PBL and BAL cells. Individuals known to be receiving azidothymidine treatment had a lower mean HIV DNA load in all cell fractions compared with those patients on no antiretroviral therapy. 相似文献
1000.
Prasse A Georges CG Biller H Hamm H Matthys H Luttmann W Virchow JC 《Clinical and experimental immunology》2000,122(2):241-248
The pathogenesis of pulmonary sarcoidosis has been related to an increased production of Th1-like cytokines. However, cytokine expression in sarcoidosis has not been systematically studied at a single-cell level. We therefore investigated the expression of IL-2, IL-4, IL-13, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) intracellularly in bronchoalveolar lavage (BAL) and peripheral blood CD3+ T lymphocytes from patients with pulmonary sarcoidosis (radiologic stage II-III, n = 8) and normal controls (n = 9) by flow cytometry. In contrast to IL-4 and IL-13, the percentage of T lymphocytes expressing intracellular IL-2 (49.3 +/- 21.3% versus 14.5 +/- 15.6%), IFN-gamma (75.5 +/- 14.9% versus 32.6 +/- 18.7%) and TNF-alpha (68.3 +/- 18.7% versus 36.8 +/- 20.8%) was significantly higher in patients with sarcoidosis than in normal controls (each P < 0.005). In contrast to BAL lymphocytes, expression of these cytokines in peripheral blood lymphocytes did not differ between patients with sarcoidosis and normal controls. Close correlations were observed between the percentages of BAL lymphocytes expressing intracellular IL-2, IFN-gamma and TNF-alpha, but not for IL-4 or IL-13. Analysis of the expression of these cytokines in T lymphocyte subsets revealed IL-2, IFN-gamma, and TNF-alpha in CD4+ as well as CD8+ T lymphocytes, suggesting a contribution of TC1 cells to the production of proinflammatory cytokines in sarcoidosis. We conclude that a Th1-like cytokine pattern can be observed in CD4+ as well as in CD8+ BAL T lymphocytes in patients with pulmonary sarcoidosis. 相似文献