全文获取类型
收费全文 | 1490篇 |
免费 | 78篇 |
国内免费 | 1篇 |
专业分类
1569篇 |
出版年
2023年 | 4篇 |
2022年 | 12篇 |
2021年 | 15篇 |
2020年 | 7篇 |
2019年 | 3篇 |
2018年 | 15篇 |
2017年 | 11篇 |
2016年 | 20篇 |
2015年 | 45篇 |
2014年 | 76篇 |
2013年 | 77篇 |
2012年 | 104篇 |
2011年 | 113篇 |
2010年 | 67篇 |
2009年 | 76篇 |
2008年 | 100篇 |
2007年 | 95篇 |
2006年 | 96篇 |
2005年 | 93篇 |
2004年 | 93篇 |
2003年 | 77篇 |
2002年 | 88篇 |
2001年 | 22篇 |
2000年 | 12篇 |
1999年 | 15篇 |
1998年 | 29篇 |
1997年 | 14篇 |
1996年 | 14篇 |
1995年 | 17篇 |
1994年 | 14篇 |
1993年 | 11篇 |
1992年 | 14篇 |
1991年 | 14篇 |
1990年 | 12篇 |
1989年 | 14篇 |
1988年 | 8篇 |
1987年 | 11篇 |
1986年 | 8篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 9篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1978年 | 4篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1974年 | 4篇 |
1971年 | 1篇 |
排序方式: 共有1569条查询结果,搜索用时 0 毫秒
81.
82.
83.
84.
85.
Regulation of the interleukin-1 receptor antagonist in THP-1 cells by ligands of the peroxisome proliferator-activated receptor gamma 总被引:5,自引:0,他引:5
Monocytes/macrophages (Mphi) play a pivotal role in the persistence of chronic inflammation and local tissue destruction in diseases such as rheumatoid arthritis and atherosclerosis. The production by Mphi of cytokines, chemokines, metalloproteinases and their inhibitors is an essential component in this process, which is tightly regulated by multiple factors. The peroxisome proliferator-activated receptors (PPARs) were shown to be involved in modulating inflammation. PPARgamma is activated by a wide variety of ligands such as fatty acids, the anti-diabetic thiazolidinediones (TZDs), and also by certain prostaglandins of which 15-deoxy-Delta(12,14)-PGJ2 (PGJ2). High concentrations of PPARgamma ligands were shown to have anti-inflammatory activities by inhibiting the secretion of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFalpha) by stimulated monocytes.The aim of this study was to determine whether PGJ2 and TZDs would also exert an immunomodulatory action through the up-regulation of anti-inflammatory cytokines such as the IL-1 receptor antagonist (IL-1Ra). THP-1 monocytic cells were stimulated with PMA, thereby enhancing the secretion of IL-1, IL-6, TNFalpha, IL-1Ra and metalloproteinases. Addition of PGJ2 had an inhibitory effect on IL-1, IL-6 and TNFalpha secretion, while increasing IL-1Ra production. In contrast, the bona fide PPARgamma ligands (TZDs; rosiglitazone, pioglitazone and troglitazone) barely inhibited proinflammatory cytokines, but strongly enhanced the production of IL-1Ra from PMA-stimulated THP-1 cells. Unstimulated cells did not respond to TZDs in terms of IL-1Ra production, suggesting that in order to be effective, PPAR ligands depend on PMA signalling. Basal levels of PPARgamma are barely detectable in unstimulated THP-1 cells, while stimulation with PMA up-regulates its expression, suggesting that higher levels of PPARgamma expression are necessary for receptor ligand effects to occur. In conclusion, we demonstrate for the first time that TZDs may exert an anti-inflammatory activity by inducing the production of the IL-1Ra. 相似文献
86.
Inheritable forms of medullary thyroid carcinoma 总被引:1,自引:0,他引:1
Medullary thyroid carcinoma (MTC) arises from parafollicular or C cells of the thyroid that produce calcitonin. It accounts for 5-10% of all thyroid cancers. Hereditary MTC represents 20-30% of all MTCs. It can be transmitted with an autosomal dominant pattern, either as a single entity, familial MTC, or it can arise as part of a multiple endocrine neoplasia (MEN) syndrome type 2A or 2B. The identification of hereditary MTC has been facilitated in recent years by the direct analysis of the ret proto-oncogene. 相似文献
87.
Increased myocardial expression of RAMP1 and RAMP3 in rats with chronic heart failure 总被引:10,自引:0,他引:10
Cueille C Pidoux E de Vernejoul MC Ventura-Clapier R Garel JM 《Biochemical and biophysical research communications》2002,294(2):340-346
Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) are potent vasodilators in humans and improved myocardial ischemia is observed after CGRP administration. Receptors for CGRP and ADM were already identified in heart. Receptor activity-modifying proteins (RAMPs) determine the ligand specificity of the calcitonin receptor-like receptor (CRLR); co-expression of RAMP1 and CRLR results in a CGRP receptor, whereas the association of RAMP2 or RAMP3 with CRLR gives an ADM receptor. As CGRP and ADM may play a beneficial role in heart failure, we investigated whether the CGRP and ADM receptors are upregulated in chronic heart failure. We have used semi-quantitative RT-PCR and Western-blot analysis to detect and quantify the mRNA and the protein of RAMP1 and RAMP3 in both atria and ventricles of failing hearts 6 months after aortic banding in rats. Our results showed for the first time an up-regulation of RAMP1 and RAMP3 mRNAs and proteins in this model of cardiac failure. No change was observed in mRNAs coding for CRLR, RAMP2, RDC1 (canine orphan receptor), and ADM. The present results suggested after congestive heart failure in adult rats, an up-regulation of the CGRP receptor (by an increase in RAMP1 that is associated with CRLR) in atria and ventricles and of ADM receptor (by increased RAMP3 expression that is associated with CRLR) in atria. These findings support a functional role for CGRP and ADM receptors to compensate the chronic heart failure in rats. 相似文献
88.
Anti-inflammatory response after infusion of p55 soluble tumor necrosis factor receptor fusion protein for severe sepsis 总被引:5,自引:0,他引:5
Butty VL Roux-Lombard P Garbino J Dayer JM Ricou B;Geneva Sepsis Network 《European cytokine network》2003,14(1):15-19
OBJECTIVES: To investigate the effects of Lenercept , a recombinant soluble TNF receptor p55 fused to an immunoglobulin heavy chain IgG1, on the balance of pro- and anti-inflammatory mediators in sepsis. DESIGN: Post hoc analysis of a subgroup of patients enrolled in a multicenter phase III, prospective, double-blind, placebo-controlled, randomized study of Lenercept in severe sepsis. SETTING: Surgical and medical intensive care units, and postoperative recovery room of a tertiary care teaching hospital. PATIENTS: A total of 57 patients were enrolled in the multicenter study in our center. Intervention: Septic patients were randomly assigned to receive either Lenercept 0.125 mg/kg or placebo. The patients were followed for up to 28 days after randomization. MEASUREMENTS AND MAIN RESULTS: Circulating levels of TNF-alpha, IL-6, TNFsR75 and IL-1Ra were measured before and after treatment. The two groups were comparable with regard to age, gender and diagnosis distribution. The total level of TNF-alpha increased significantly in treated patients, compared to patients receiving placebo. The levels of the other inflammatory mediators did not differ between the two groups CONCLUSIONS: Lenercept -treated patients experienced a protracted TNF-alpha half-life, leading to higher total TNF-alpha levels throughout the study. However, the treatment had no effects on anti-inflammatory mediators. Therefore, peripheral inflammatory processes might not have been significantly modified by the treatment. This might account for the lack of efficacy this treatment in septic patients 相似文献
89.
Polarisation of prokaryotic chromosomes 总被引:1,自引:0,他引:1
In many prokaryotes, asymmetrical mutational or selective pressures have caused compositional skews between complementary strands of replication arms, especially sensitive in the distribution of guanine and cytosine. In Escherichia coli, most of the guanine/cytosine skew is caused by mutation rates differing on leading and lagging strands, but contribution of skewed functionally important guanine-rich motifs (Chi and Rag sites), which control chromosome repair or positioning, is noticeable. Interference between replication and gene expression plays a minor role. The situation may be different in other bacteria. Studies of chromosome processing and bacterial taxonomy might profit from consideration of chromosome polarisation. 相似文献
90.
A simple and convenient microtiter plate assay for the detection of bactericidal antibodies to Vibrio cholerae O1 and Vibrio cholerae O139 总被引:1,自引:0,他引:1
Boutonnier A Dassy B Duménil R Guénolé A Ratsitorahina M Migliani R Fournier JM 《Journal of microbiological methods》2003,55(3):745-753
It is believed that the correlate of protection for cholera can be determined by the serum vibriocidal assay. The currently available vibriocidal assays, based on the conventional agar plating technique, are labor intensive. We developed a simple and convenient microtiter plate assay for the detection of vibriocidal antibodies that is equally as efficient for Vibrio cholerae O1 and for V. cholerae O139. The addition of succinate and neotetrazolium made it possible to measure the growth of surviving bacterial target cells by monitoring a color change. We evaluated assay parameters (target strains, growth of target cells, complement source and concentration) that may affect the reproducibility of the method for V. cholerae O139. The results obtained with the microtiter plate assay were uniformly similar to those obtained with the conventional agar plating assay, when testing both the Inaba and Ogawa serotypes of V. cholerae O1. The microtiter plate assay was also convenient for measuring the activity of animal sera and mouse monoclonal antibodies. 相似文献