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1.
Background and aimsIntermittent fasting reduces risk of interrelated cardiometabolic diseases, including type 2 diabetes and heart failure (HF). Previously, we reported that intermittent fasting reduced homeostasis model assessment of insulin resistance (HOMA-IR) and Metabolic Syndrome Score (MSS) in the WONDERFUL Trial. Galectin-3 may act to reduce insulin resistance. This post hoc evaluation assessed whether intermittent fasting increased galectin-3.Methods and resultsThe WONDERFUL Trial enrolled adults ages 21–70 years with ≥1 metabolic syndrome features or type 2 diabetes who were not taking anti-diabetic medication, were free of statins, and had elevated LDL-C. Subjects were randomized to water-only 24-h intermittent fasting conducted twice-per-week for 4 weeks and once-per-week for 22 weeks or to a parallel control arm with ad libitum energy intake. The study evaluated 26-week change scores of galectin-3 and other biomarkers. Overall, n = 67 subjects (intermittent fasting: n = 36; control: n = 31) completed the trial and had galectin-3 results. At 26-weeks, the galectin-3 change score was increased by intermittent fasting (median: 0.793 ng/mL, IQR: ?0.538, 2.245) versus control (median: ?0.332 ng/mL, IQR: ?0.992, 0.776; p = 0.021). Galectin-3 changes correlated inversely with 26-week change scores of HOMA-IR (r = ?0.288, p = 0.018) and MSS (r = ?0.238, p = 0.052). Other HF biomarkers were unchanged by fasting.ConclusionA 24-h water-only intermittent fasting regimen increased galectin-3. The fasting-triggered galectin-3 elevation was inversely correlated with declines in HOMA-IR and MSS. This may be an evolutionary adaptive survival response that protects human health by modifying disease risks, including by reducing inflammation and insulin resistance.Trial registrationClinicaltrials.gov, NCT02770313 (registered on May 12, 2016; first subject enrolled: November 30, 2016; final subject's 26-week study visit: February 19, 2020).  相似文献   
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Background and aimsAlthough antithrombotic treatments are established for coronary artery disease (CAD), they increase the bleeding risk, especially in malnourished patients. The total thrombus-formation analysis system (T-TAS) is useful for the assessment of thrombogenicity in CAD patients. Here, we examined the relationships among malnutrition, thrombogenicity and 1-year bleeding events in patients undergoing percutaneous coronary intervention (PCI).Methods and resultsThis was a retrospective analysis of 300 consecutive CAD patients undergoing PCI. Blood samples obtained on the day of PCI were used in the T-TAS to compute the thrombus formation area under the curve. We assigned patients to two groups based on the geriatric nutritional risk index (GNRI): 102 patients to the lower GNRI group (≤98), 198 patients to the higher GNRI group (98<). The primary endpoint was the incidence of 1-year bleeding events defined by Bleeding Academic Research Consortium criteria types 2, 3, or 5. The T-TAS levels were lower in the lower GNRI group than in the higher GNRI group. Kaplan-Meier analysis showed worse 1-year bleeding event-free survival in the lower GNRI group compared with the higher GNRI group. The combined model of the GNRI and the Academic Research Consortium for High Bleeding Risk (ARC-HBR) had good calibration and discrimination for bleeding risk prediction. In addition, having a lower GNRI and ARC-HBR positivity was associated with 1-year bleeding events.ConclusionA lower GNRI could reflect low thrombogenicity evaluated by the T-TAS and determine bleeding risk in combination with ARC-HBR positivity.  相似文献   
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Background and aimsThe prevalence of type 2 diabetes (T2D) in Italy is increasing and cardiovascular disease (CVD) represents the leading cause of death in this population. CAPTURE was a multinational, multicentre, non-interventional, cross-sectional study assessing the prevalence of CVD, atherosclerotic CVD (AsCVD) and CVD subtypes among patients with T2D, across 13 countries. Here we report the results from Italy.Methods and resultsOverall, 816 patients with T2D (median age, 69 years [interquartile range: 62–75]; median duration of diabetes, 11.2 years [interquartile range: 5.7–18.7]) were recruited during routine clinical visits at secondary care centres in Italy between December 2018–September 2019. The prevalence of CVD was estimated at 38.8%, largely accounted for by AsCVD (33.1%). The most prevalent CVD subtype was coronary heart disease (20.8%), followed by carotid artery disease (13.2%). Most patients (85.9%) were prescribed oral glucose-lowering agents (GLAs), particularly biguanide (76.7%). Insulin use was higher in patients with CVD (41.3%) than in patients without CVD (32.9%). Sodium-glucose co-transporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were prescribed to 20.2% vs 14.6%, and 14.5% vs 16.6% of patients with CVD compared to those without CVD, respectively.ConclusionThe results show that, in Italy, more than one in three patients with T2D attending secondary care centres have CVD, 85% of whom have AsCVD, yet only a minority are treated with SGLT2is and GLP-1 RAs, in discordance with the recommendations of current national and international guidelines.  相似文献   
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Background and aimBased on the emerging role of Kruppel-like factor 6 (KLF6) in lipid metabolism, we examined whether there is a relationship between the KLF6 rs3750861 genetic variant and plasma ceramide levels in people with type 2 diabetes mellitus (T2DM).Methods and resultWe measured six previously identified plasma ceramides, which have been associated with increased cardiovascular risk [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] amongst 101 Caucasian post-menopausal women with T2DM, who consecutively attended our diabetes outpatient service during a 3-month period. Plasma ceramides were measured by targeted liquid chromatography-tandem mass spectrometry assay. Genotyping of the KLF6 rs3750861 polymorphism was performed by TaqMan-Based RT-PCR system.Overall, 87 (86.1%) patients had KLF6 rs3750861 C/C genotype and 14 (13.9%) had C/T or T/T genotypes. After adjustment for age, diabetes-related variables, use of lipid-lowering drugs and other potential confounders, patients with C/T or T/T genotypes had higher plasma Cer(d18:1/18:0) (0.159 ± 0.05 vs. 0.120 ± 0.04 μmol/L, p = 0.012), Cer(d18:1/20:0) (0.129 ± 0.04 vs. 0.098 ± 0.03 μmol/L, p = 0.008), and Cer(d18:1/24:1) (1.236 ± 0.38 vs. 0.978 ± 0.36 μmol/L, p = 0.032) compared with those with C/C genotype.ConclusionsThe C/T or T/T genotypes of rs3750861 in the KLF6 gene were closely associated with higher levels of specific plasma ceramides in post-menopausal women with T2DM.  相似文献   
6.
Background and objectiveThere is a growing body of evidence that the equations used to estimate the glomerular filtration rate (GFR) are not suitable in critically ill patients, a population whose GFR fluctuates continuously. Glomerular filtration is usually estimated by measuring urine creatinine clearance (CrCl) at various time points. The aim of our study was to evaluate the performance of the most widely used GFR calculators in the subpopulation of critically ill patients admitted for severe trauma, and to compare the results against determinations of CrCl in urine collected over a 4-hour period (4h-CrCl).Material and methodsObservational study in patients hospitalized for severe trauma. We measured the 4h-CrCl and estimated GFR using the Cockcroft-Gault, modified Jelliffe, MDRD, t-MDRD, and CKD-EPI equations, adjusting the results for body surface area (BSA) (ml/min/1.73m2). Data were analysed using R version 4.0.4.ResultsA total of 85 patients were included. Median age was 51 years, and 68 were men (78.82%). The mean BSA-adjusted 4h-CrCl (4h-ClCr/1.73 m2) was 84.5 ml/min/1.73 m2. We found that GFR estimated using the t-MDRD equation correlated significantly with 4h-CrCl/1.73 m2. The Cockcroft-Gault equation correlated significantly with 4h-CrCl/1.73 m2 when GFR was greater than 130 ml/min/m2.ConclusionsIn ICU patients, glomerular filtration can be reliably estimated by determining urine CrCl, but GFR calculators are not accurate in this population.  相似文献   
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ObjectivesThe reduction of postoperative acute kidney injury in patients undergoing cardiopulmonary bypass surgery using an oxygen delivery-guided perfusion strategy (oxygen delivery strategy) for cardiopulmonary bypass management compared with a fixed flow perfusion (conventional strategy) remains controversial. The purpose of this study was to determine whether a oxygen delivery strategy would reduce the incidence of postoperative acute kidney injury in patients undergoing cardiopulmonary bypass surgery.MethodsWe randomly enrolled 300 patients undergoing cardiopulmonary bypass surgery. Patients were randomly assigned to a oxygen delivery strategy (maintaining a oxygen delivery index value >300 mL/min/m2 through pump flow adjustments during cardiopulmonary bypass) or a conventional strategy (a target pump flow was determined on the basis of the body surface area). The primary end point was the development of acute kidney injury. Secondary end points were the red blood cell transfusion rate and number of red blood cell units, intubation time, postoperative length of stay in the intensive care unit and the hospital, predischarge estimated glomerular filtration rate, and hospital mortality.ResultsAcute kidney injury occurred in 20 patients (14.6%) receiving the oxygen delivery strategy and in 42 patients (30.4%) receiving the conventional strategy (relative risk, 0.48; 95% confidence interval, 0.30-0.77; P = .002). The secondary end points were not significantly different between strategies. In a prespecified subgroup analysis of patients who had nadir hematocrit less than 23% or body surface area less than 1.40 m2, the oxygen delivery strategy seemed to be superior to the conventional strategy and the existence of quantitative interactions was suggested.ConclusionsAn oxygen delivery strategy for cardiopulmonary bypass management was superior to a conventional strategy with respect to preventing the development of acute kidney injury.  相似文献   
10.
ObjectiveTo evaluate whether the serum C-reactive protein to albumin ratio (CAR) could be used for risk stratification of patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS).Patients and MethodsFrailty is a predictor of poor outcomes in patients undergoing AS interventions. The CAR reflects key components of frailty (systemic inflammation and nutrition) and could potentially be implemented into assessment and management strategies for patients with AS. From March 1, 2010, through February 29, 2020, 1836 patients were prospectively enrolled in an observational TAVR database. Patients (prospective development cohort, n=763) were grouped into CAR quartiles to compare the upper quartile (CAR Q4) with the lower quartiles (CAR Q1-3). Primary end point was all-cause mortality. Results were verified in an independent retrospective cohort (n=1403).ResultsThe CAR Q4 had a higher prevalence of impaired left ventricular function, atrial fibrillation, diabetes, and cerebrovascular disease and a higher median logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) vs CAR Q1-3. After median follow-up of 15.0 months, all-cause mortality was significantly higher in CAR Q4 vs CAR Q1-3 (P<.001). In multivariable analyses, risk factors for all-cause mortality were CAR Q4 (>0.1632; hazard ratio, 1.45; 95% confidence interval, 1.05 to 2.00; P=.03), N-terminal pro–B-type natriuretic peptide Q4 (>3230 pg/mL [to convert to ng/L, multiply by 1), high-sensitivity troponin T Q4 (>0.0395 ng/mL [to convert to μg/L, multiply by 1]), above-median logistic EuroSCORE (16.1%), myocardial infarction, Acute Kidney Injury Network stage 3, and life-threatening bleeding.ConclusionElevated CAR was associated with increased risk of all-cause mortality in patients undergoing transfemoral TAVR. The CAR, a simple, objective tool to assess frailty, could be incorporated into assessing patients with AS being considered for TAVR.  相似文献   
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