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Resveratrol is a polyphenolic flavonoid found in a diversity of plants, especially berry fruits and is a popular nutritional supplement. It is known to have antioxidant, anti-inflammatory, and anticarcinogenic properties. Recently, additional evidence has been found that resveratrol is beneficial to metabolic and cardiovascular health and may increase the life expectancy of various organisms. These biological effects are widely believed to be due to the ability of resveratrol to activate silent mating-type information regulation 2 homolog 1, a nicotinamide adenine dinucleotide-dependent deacetylase. However, other research has shown that 5′-adenosine monophosphate–activated kinase and not silent mating-type information regulation 2 homolog 1 may be the target of resveratrol. A recent study reported that resveratrol directly inhibits cyclic adenosine monophosphate–specific phosphodiesterases and then activates 5′-adenosine monophosphate–activated kinase. Therefore, the mechanism underlying the diverse nutritional and therapeutic activities of resveratrol needs to be further explored. Furthermore, the optimal dose and possible adverse effects of resveratrol in humans are completely clear. The purpose of this review is to present some of the newly discovered biological effects of resveratrol, including autophagy and stem cell regulation, and research opportunities for the application of resveratrol in cardiovascular and metabolic health. Described herein is the recent understanding of the mechanism of action of resveratrol and future research directions to ascertain the potential of this flavonoid that is present in food.  相似文献   
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目的分析老年下肢动脉闭塞患者动脉造影(DSA)的临床及病变特征,并测定血清高敏C反应蛋白(hs-CRP)水平,探讨hs-CRP检测的诊断意义。方法回顾性地分析第三军医大学老年科2008年1月至2012年12月间收治的41例老年下肢动脉闭塞患者的临床资料。分析临床特点、血压水平、性别差异、DSA的病变特点、hs-CRP水平及其与DSA造影结果的相关性。结果下肢动脉造影提示老年患者多存在多支、弥漫性病变,侧支循环形成差,症状较重,多以保守治疗为主。老年男性患者血压水平无明显升高,老年女性患者的收缩压水平高于男性患者,老年下肢动脉粥样硬化患者CRP明显增高,但无明显性别差异,也与病变的严重程度无关(P〈0.05)。结论DSA检测显示老年下肢动脉闭塞的患者病变有其独特性,血压升高水平有性别差异,hs-CRP在多数患者中有升高,但是无性别差异,也不能完全评估严重程度。  相似文献   
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Endothelin (ET)-1 and suppressor of cytokine signaling (SOCS)-3 were respectively found to regulate energy metabolism and hormone signaling in fat cells. Although ET-1 can also regulate the expression of SOCS-3-stimulating hormones, it is still unknown whether ET-1 regulates SOCS-3 gene expression. This study investigated the pathways involved in ET-1's modulation of SOCS-3 gene expression in 3T3-L1 adipocytes. ET-1 upregulated SOCS-3 mRNA and protein expression in dose- and time-dependent manners. The concentration of ET-1 that increased SOCS-3 mRNA levels by 250-400% was ~100nM with 2-4h of treatment. Treatment with actinomycin D prevented ET-1-stimulated SOCS-3 mRNA expression, suggesting that the effect of ET-1 requires new mRNA synthesis. Pretreatment with the ET type A receptor (ET(A)R) antagonist, BQ-610, but not the ET type B receptor (ET(B)R) antagonist, BQ-788, prevented the stimulatory effect of ET-1 on SOCS-3 gene expression. The specific inhibitors of either MEK1 (U-0126 and PD-98059), JAK (AG-490), JNK (SP-600125), or PI3K (LY-294002 and wortmannin) reduced ET-1-increased levels of SOCS-3 mRNA and respectively inhibited ET-1-stimulated activities of MEK1, JAK, JNK, and PI3K. These results imply that the ET(A)R, ERK, JAK, JNK, and PI3K are functionally necessary for ET-1's stimulation of SOCS-3 gene expression. Moreover, ET-1 was observed to upregulate expressions of SOCS-1, -2, -3, -4, -5, and -6 mRNAs, but not SOCS-7 or cytokine-inducible SH2-containing protein-1 mRNAs. This suggests that ET-1 selectively affects particular types of SOCS family members. Changes in SOCS gene expressions induced by ET-1 may help explain the mechanism by which ET-1 modulates hormone signaling of adipocytes.  相似文献   
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Yuan QY  Zhu ZW  Wang Z  Wang XM  Li XS  Huang J  Si LY 《Heart and vessels》2012,27(3):316-326
This study presents a novel method that direct intramyocardial injection of low-dose plasmid DNA and microbubbles combined with insonation could further augment gene expression in normal and ischemic canine myocardium. Plasmids encoding enhanced green fluorescent protein (pEGFP) and hepatocyte growth factor (pHGF) (500???g) were individually mixed with 0.5?ml of microbubble solution (MB) and injected into the normal or acute ischemic canine myocardium. The dogs in the plasmid?+?MB/US group underwent insonation (US). Other dogs were randomly divided into three treatment groups: plasmid and insonation, plasmid and MB injection, and plasmid injection only. The EGFP and HGF mRNA expressions were assessed in the myocardium at the injection site and at sites 0.5 and 1?cm remote from the injection site. Compared to plasmid transfer alone, a mean 13.4-fold enhancement of gene expression was achieved in the EGFP?+?MB/US group at 48?h (p?<?0.01). HGF mRNA expression in ischemic zones was markedly elevated after 28?days, with a mean 9.0-fold enhancement in the HGF?+?MB/US group (p?<?0.01). EGFP protein expression was detected in the normal myocardium at 1?cm remote from the injection site in the EGFP?+?MB/US group. Similarly, HGF protein expression was detected in the ischemic myocardium at 0.5?cm remote from the injection site in the HGF?+?MB/US group. These findings indicate that the radius of gene expression was partly extended in the two plasmid?+?MB/US groups. The capillary density increased from 20.9?±?5.3/mm2 in control myocardial infarction dogs without treatment to 126.7?±?38.2/mm2 in the HGF?+?MB/US group (p?<?0.01). Taken together, the present data demonstrate that direct intramyocardial injection of an angiogenic gene and microbubbles combined with insonation can augment gene expression and angiogenesis. Consequently, this strategy may be a useful tool for gene therapy of ischemic heart disease.  相似文献   
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The aim of this study was to assess the overall and cause-specific incidences of diabetic hand syndromes (DHS) in patients with diabetes mellitus (DM) by using age and sex stratifications.The DM and control cohorts comprised 606,152 patients with DM and 609,970 age- and sex-matched subjects, respectively, who were followed up from 2000 to 2008. We estimated the incidence densities (IDs) of overall and cause-specific DHS, namely carpal tunnel syndrome (CTS), stenosing flexor tenosynovitis (SFT), limited joint mobility (LJM), and Dupuytren disease (DD), and calculated the hazard ratios (HRs) of DHS in relation to DM by using a Cox proportional hazards model with adjustment for potential confounders.Over a 9-year period, 51,207 patients with DM (8.45%) and 39,153 matched controls (6.42%) sought ambulatory care visits for various DHS, with an ID of 117.7 and 80.7 per 10,000 person-years, respectively. The highest cause-specific ID was observed for CTS, followed by SFT, LJM, and DD, regardless of the diabetic status. After adjustment for potential confounders, patients with DM had a significantly high HR of overall DHS (1.51, 95% confidence interval [CI] = 1.48–1.53). Men and women aged <35 years had the highest HR (2.64, 95% CI = 2.15–3.24 and 2.99, 95% CI = 2.55–3.50, respectively). Cause-specific analyses revealed that DM was more strongly associated with SFT (HR = 1.90, 95% CI = 1.86–1.95) and DD (HR = 1.83, 95% CI = 1.39–2.39) than with CTS (HR = 1.31, 95% CI = 1.28–1.34) and LJM (HR = 1.24, 95% CI = 1.13–1.35).Men and younger patients with DM have the highest risk of DHS. Certain hand syndromes, such as SFT and DD, were more strongly associated with DM than with other syndromes and require the attention of clinicians.  相似文献   
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Background and objective:   The aim of this study was to characterize the changes in neutrophils and cytokines in BAL fluid following acute lung injury (ALI), and to determine the protective effect of post-injury treatment with IL-10.
Methods:   A rat model of ALI was established by evenly spraying LPS (16 mg/kg) into the lungs followed by observation for 48 h. Histological changes and the kinetics of neutrophil infiltration were evaluated in the injured lungs. The cytokines (TNF-α, IL-6, IL-10 and interferon-γ) and macrophage-inflammatory protein (MIP-2) were measured in BAL fluid by ELISA. The activation of BAL fluid neutrophils was investigated after treatment with IL-10 in vitro . The protective effect on histology and MIP-2 levels of intra-tracheal instillation of IL-10 12 and 16 h after LPS treatment was studied in vivo.
Results:   Intra-tracheal instillation of LPS caused significant lung injury and the activation of neutrophils. The levels of TNF-α and IL-6 in BAL fluid peaked at 8 and 16 h after LPS instillation respectively. IL-10 levels reached a maximum at 16–24 h, at the beginning of resolution of tissue injury. IL-10 inhibited the activation of neutrophils in vitro and MIP-2 induction in vivo . IL-10 had a protective effect if it was administered 12 but not 16 h after LPS.
Conclusions:   Neutrophils appeared to play an important role in ALI. Time-dependent treatment with IL-10 after intra-tracheal instillation of LPS was effective in protecting rats from ALI, probably by suppressing pulmonary infiltration with activated neutrophils.  相似文献   
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ObjectiveGenetic studies of complex human diseases rely heavily on the epidemiologic association paradigm, particularly the population-based case–control designs. This study aims to compare the matching effectiveness in terms of bias reduction between exposure matching and stratum matching.Study Design and SettingFormulas for population stratification bias were derived. An index of matching effectiveness was constructed to compare the two types of matching.ResultsIt was found that exposure matching can paradoxically increase the magnitude of population stratification bias sometimes, whereas stratum matching can guarantee to reduce it.ConclusionThe authors propose two simple rules for genetic association studies: (a) to match on anything that helps to delineate population strata such as race, ethnicity, nationality, ancestry, and birthplace and (b) to match on an exposure only when it is a strong predictor of the disease and is expected to have great variation in prevalence across population strata.  相似文献   
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