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1.
Platelet activation is found in inflammatory conditions and implicated in the pathogenesis of chronic medical conditions, such as atherosclerosis, coronary vascular disease, cerebrovascular disease, and diabetes mellitus (DM). HbA1c is inversely related to vitamin D25 levels in individuals with and without DM. This study aimed to determine the relation between platelet aggregation, vitamin D and HbA1c among healthy individuals and those with Type 2 DM (T2DM). The direct effect of vitamin D1, 25 (calcitriol) on platelet aggregation was also investigated. The study included four groups: A. normoglycemic Control group: HbA1c<5.7%; B. Pre-diabetes (DM): 5.7% ≥ HbA1c ≤ 6.4%; C. DM on aspirin therapy: HbA1c>6.4%(+)Asp.; and D. DM not on aspirin therapy: HbA1c > 6.4%(?)Asp. Platelet aggregation was tested with and without calcitriol or saline pre-treatment, using collagen or adenosine diphosphate (ADP) as agonists. Platelet aggregation was higher in DM(?)Asp group compared to normoglycemic and DM(+)Asp, and higher, but not significant compared to pre-DM. The entire study population exhibited negative correlation between HbA1c and serum concentration of vitamin D25. Excluding DM(+)Asp, aggregation induced by collagen was significantly higher in patients with insufficient (<76 nmol/L) vitamin D25 compared to sufficient (≥76 nmol/L) vitamin D25. In this cohort, a negative correlation was found between serum concentrations of vitamin D25 and collagen-induced percent maximum (%max) aggregation and area under curve (AUC) aggregation. In the DM(?)Asp group, collagen-induced aggregation was reduced by approximately 25% after calcitriol treatment. Calcitriol decreased ADP-induced aggregation of control and DM(+)Asp groups to approximately 85% of saline treatment. We conclude that glycemic control is inversely associated with high platelet aggregation and low vitamin D25 levels. This elevated aggregation could be regulated by a novel, direct effect of calcitriol, indicating a beneficial effect of vitamin D on vascular complications related to diabetes. We offer a possible non-genomic mechanism for the vitamin D/Vitamin D receptor (VDR) pathway.  相似文献   
2.
Chitosan nanoparticles (CSNPs) have potential applications in stem cell research. In this study, ex vivo cytotoxicity of CSNPs on mouse bone marrow-derived (MBMCs) hematopoietic stem and progenitor cells (HSPCs) was determined. MBMCs were exposed to CSNPs of different particle sizes at various concentrations for up to 72 h. Cytotoxicity effect of CSNPs on MBMCs was determined using MTT, Live/Dead Viability/Cytotoxicity assays and flow cytometry analysis of surface antigens on HSCs (Sca-1+), myeloid-committed progenitors (CD11b+, Gr-1+), and lymphoid-committed progenitors (CD45+, CD3e+). At 24 h incubation, MBMCs' viability was not affected by CSNPs. At 48 and 72 h, significant reduction was detected at higher CSNPs concentrations. Small CSNPs (200 nm) significantly reduced MBMCs' viability while medium-sized particle (∼400 nm) selectively promoted MBMCs growth. Surface antigen assessment demonstrated lineage-dependent effect. Significant decrease in Sca-1+ cells percentage was observed for medium-sized particle at the lowest CSNPs concentration. Meanwhile, reduction of CD11b+ and Gr-1+ cells percentage was detected at high and intermediate concentrations of medium-sized and large CSNPs. Percentage of CD45+ and CD3e+ cells along with ROS levels were not significantly affected by CSNPs. In conclusion, medium-sized and large CSNPs were relatively non-toxic at lower concentrations. However, further investigations are necessary for therapeutic applications.  相似文献   
3.
背景:通过检测CYP2C19基因分型可评估冠状动脉内支架置入患者对氯吡格雷反应性的高低,但目前国内尚缺乏通过检测CYP2C19基因分型指导分叉病变部位支架置入后抗血小板治疗的临床应用。目的:根据CYP2C19基因分型结果,优化冠状动脉分叉病变支架置入后抗血小板治疗方案的效果。方法:纳入136例冠状动脉分叉病变支架置入患者,于支架置入前进行阿司匹林联合氯吡格雷抗血小板治疗,7 d后检测CYP2C19基因分型。若CYP2C19基因分型为*1/*1的作为合格组,支架置入后服用氯吡格雷75 mg/d;若CYP2C19基因分型为*2/*2、*2/*3、*3/*3的作为不合格组,再随机分为2组,一组为常规剂量组,支架置入后即保持氯吡格雷75 mg/d治疗不变,另一组为大剂量组,即增加氯吡格雷剂量为150 mg/d长期服用。随访9个月记录主要心脏不良事件和出血事件发生情况。结果与结论:发生主要心脏不良事件14例中,合格组6例(7.9%)、常规剂量组6例(17.7%)、大剂量组2例(7.7%),合格组发生率明显低于常规剂量组(P<0.05),提示CYP2C19基因分型有较好预测主要心脏不良事件的价值;大剂量组发生率明显小于常规剂量组(P<0.05),说明在CYP2C19基因分型监测下增加抗血小板药物剂量,能明显降低主要心脏不良事件的发生率;大剂量组发生率与合格组比较差异无显著性意义(P>0.05),提示通过检测CYP2C19基因分型,优化氯吡格雷剂量可达到与合格组相同的临床效果。3组出血事件发生率比较差异无显著性意义(P>0.05),提示通过检测CYP2C19基因分型抗血小板治疗不会增加出血风险。  相似文献   
4.
Protein aggregation is normally associated with amyloidosis, namely motor neurone, Alzheimer’s, Parkinson’s or prion diseases. However, recent results have unveiled a concept of gradual increase of protein aggregation associated with the ageing process, apparently not necessarily associated with pathological conditions. Given that protein aggregation is sufficient to activate stress-response and inflammation, impairing protein synthesis and quality control mechanisms, the former is assumed to negatively affect cellular metabolism and behaviour. In this review the state of the art in protein aggregation research is discussed, namely the relationship between pathology and proteostasis. The role of pathology and ageing in overriding protein quality-control mechanisms, and consequently, the effect of these faulty cellular processes on pathological and healthy ageing, are also addressed.  相似文献   
5.
BackgroundThere are several prognostic models to estimate the risk of mortality after surgery for active infective endocarditis (IE). However, these models incorporate different predictors and their performance is uncertain.ObjectiveWe systematically reviewed and critically appraised all available prediction models of postoperative mortality in patients undergoing surgery for IE, and aggregated them into a meta-model.Data sourcesWe searched Medline and EMBASE databases from inception to June 2020.Study eligibility criteriaWe included studies that developed or updated a prognostic model of postoperative mortality in patient with IE.MethodsWe assessed the risk of bias of the models using PROBAST (Prediction model Risk Of Bias ASsessment Tool) and we aggregated them into an aggregate meta-model based on stacked regressions and optimized it for a nationwide registry of IE patients. The meta-model performance was assessed using bootstrap validation methods and adjusted for optimism.ResultsWe identified 11 prognostic models for postoperative mortality. Eight models had a high risk of bias. The meta-model included weighted predictors from the remaining three models (EndoSCORE, specific ES-I and specific ES-II), which were not rated as high risk of bias and provided full model equations. Additionally, two variables (age and infectious agent) that had been modelled differently across studies, were estimated based on the nationwide registry. The performance of the meta-model was better than the original three models, with the corresponding performance measures: C-statistics 0.79 (95% CI 0.76–0.82), calibration slope 0.98 (95% CI 0.86–1.13) and calibration-in-the-large –0.05 (95% CI –0.20 to 0.11).ConclusionsThe meta-model outperformed published models and showed a robust predictive capacity for predicting the individualized risk of postoperative mortality in patients with IE.Protocol registrationPROSPERO (registration number CRD42020192602).  相似文献   
6.

Background

Sudden infant death syndrome (SIDS) is a leading cause of postneonatal mortality. Genetic heart diseases (GHDs) underlie some cases of SIDS.

Objectives

This study aimed to determine the spectrum and prevalence of GHD-associated mutations as a potential monogenic basis for SIDS.

Methods

A cohort of 419 unrelated SIDS cases (257 male; average age 2.7 ± 1.9 months) underwent whole exome sequencing and a targeted analysis of 90 GHD-susceptibility genes. The yield of “potentially informative,” ultra-rare variants (minor allele frequency <0.00005) in GHD-associated genes was assessed.

Results

Overall, 53 of 419 (12.6%) SIDS cases had ≥1 “potentially informative,” GHD-associated variant. The yield was 14.9% (21 of 141) for mixed-European ancestry cases and 11.5% (32 of 278) for European ancestry SIDS cases. Infants older than 4 months were more likely to host a “potentially informative” GHD-associated variant. There was significant overrepresentation of ultra-rare nonsynonymous variants in European SIDS cases (18 of 278 [6.5%]) versus European control subjects (30 of 973 [3.1%]; p = 0.013) when combining all 4 major cardiac channelopathy genes (KCNQ1, KCNH2, SCN5A, and RYR2). According to the American College of Medical Genetics guidelines, only 18 of 419 (4.3%) SIDS cases hosted a “pathogenic” or “likely pathogenic” variant.

Conclusions

Less than 15% of more than 400 SIDS cases had a “potentially informative” variant in a GHD-susceptibility gene, predominantly in the 4- to 12-month age group. Only 4.3% of cases possessed immediately clinically actionable variants. Consistent with previous studies, ultra-rare, nonsynonymous variants within the major cardiac channelopathy-associated genes were overrepresented in SIDS cases in infants of European ethnicity. These findings have major implications for the investigation of SIDS cases and families.  相似文献   
7.
目的通过探讨体外不同浓度50am葡聚糖包裹磁性纳米材料的致栓性,评价其作为药物载体的发伞性。方法以PBS为对照组,将0.02mg/ml、0.1mg/ml、0.5mg/ml浓度的磁性纳米颗粒与血浆或全血在体外共孵育,检测血小扳聚集率、凝血功能、血凝块质量及血栓弹力图。结果(1)PBS组、0.02mg/ml SPIO组、0.1mg/ml SPIO组及0.5mg/ml SPIO组血小板聚集率分别为67.3±5.9%、68.3±4.5%、66.2±5.5%及69.5±5.9%(P〉0.05);(2)4组的APTT值分别为28.1±2.7S、28.5±2.4S、28.2±2.5S及29.1±3.6S(P〉0.05),PT值和TT值各组间也无统计学差异(P〉0.05)。(3)血栓弹力图各参数(反应凝血功能的R时间、反应纤维蛋自原功能的K时间及α角、反应血小板功能的MA值、凝血综合指数CI),各组间比较差异均无显著性(P〉0.05)。(4)4组的血凝块质量分别为759.6±38.7mg、758.8±47.2mg、769.8±39.2mg和766.8±40.8mg,组问比较无统计学差异(P〉0.05)。结论50nm葡聚糖包裹磁性纳米材料在一定浓度范围内(0.02mg/ml-0.5mg/ml)对血小板聚集、凝血功能、血凝块质量及血栓弹力图均无明显影响,表明其无致栓性.血液相容性较好,可较为安全的应用于血栓性疾病的研究。  相似文献   
8.
Heart valve prosthesis unquestionably improve quality of life and survival of patients with severe valvular heart disease, but the need for antithrombotic therapy to prevent thromboembolic complications is a major challenge to clinicians and their patients. Of the articles analyzed, most were retrospective series of cases or historical cohorts obtained from the database. The few published randomized trials showed no statistical power to assess the primary outcome of death or thromboembolic event. In this article, we decided to perform a systematic literature review, in an attempt to answer the following question: what is the best antithrombotic strategy in the first three months after bioprosthetic heart valve implantation (mitral and aortic)?After two reviewers applying the extraction criteria, we found 1968 references, selecting 31 references (excluding papers truncated, which combined bioprosthesis with mechanical prosthesis, or without follow-up).Based on this literature review, there was a low level of evidence for any antithrombotic therapeutic strategy evaluated. It´s therefore interesting to use aspirin 75 to 100 mg / day as antithrombotic strategy after bioprosthesis replacement in the aortic position, regardless of etiology, for patients without other risk factors such as atrial fibrillation or previous thromboembolic event. In the mitral position, the risk of embolism, although low, is more relevant than in the aortic position, according to published series and retrospective cohorts comprised mostly of elderly non-rheumatic patients.The current evidence is limited to have a consistent and safe level of evidence regarding the best therapeutic strategy. Based on these studies, 75 to 100 mg/day of aspirin is interesting as antithrombotic strategy after implantation of aortic bioprosthesis, regardless of etiology, for patients with no other risk factors such as atrial fibrillation or previous thromboembolic event. As for mitral bioprosthesis, the risk of embolism, although low, is more relevant than in the aortic position, according to published series and retrospective cohorts - usually elderly non rheumatic patients.  相似文献   
9.
Apart from their role in hemostasis and thrombosis, platelets are involved in many other biological processes such as wound healing and angiogenesis. Percutaneous coronary intervention is a highly thrombogenic procedure inducing platelets and monocytes activation through endothelial trauma and contact activation by intravascular devices. Platelet P2Y12 receptor activation by adenosine diphosphate facilitates non-ADP agonist-mediated platelet aggregation, dense granule secretion, procoagulant activity, and the phosphorylation of several intraplatelet proteins, making it an ideal drug target. However, not all compounds that target the P2Y12 receptor have similar efficacy and safety profiles. Despite targeting the same receptor, the unique pharmacologic properties of each of these P2Y12 receptor-directed compounds can lead to very different clinical effects.  相似文献   
10.
Blood rheology and aging   总被引:1,自引:0,他引:1  
The flow properties of blood play significant roles in tissue perfusion by contributing to hydrodynamic resistance in blood vessels. These properties are influenced by pathophysiological processes, thereby increasing the clinical relevance of blood rheology information. There is well-established clinical evidence for impaired blood fluidity in humans of advanced age, including enhanced plasma and whole blood viscosity, impaired red blood cell (RBC) deformability and enhanced RBC aggregation. Increased plasma fibrinogen concentration is a common finding in many studies owing to the pro-inflammatory condition of aged individuals; this finding of increased fibrinogen concen-tration explains the higher plasma viscosity and RBC aggregation in elderly subjects. Enhanced oxidant stress in advanced age is also known to contribute to altered blood fluidity, with RBC deformability being an important determinant of blood viscosity. Several studies have shown that physical activity may improve the hemorheological picture in elderly subjects, yet well-designed observational and mechanistic studies are required to determine the specific effects of regular exercise on hemorheological parameters in healthy and older individuals.  相似文献   
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