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Background
Glucocorticoids play essential roles in the treatment of childhood acute lymphoblastic leukaemia (ALL); however, treatment with these agents can result in severe side-effects. This study, the first of its kind in a Saudi population, investigates associations of ABCB1 gene polymorphisms (pharmacodynamics and pharmacokinetic) with the development of toxicity and side effects (glucose abnormality, liver toxicity and infection) in a small population of Saudi children with ALL.Methods
Three single nucleotide polymorphisms (SNPs) of the ABCB1 gene (rs 3213619 T129C, rs 2032582 G2677T and rs1045642 C3435T) were analysed in 70 Saudi children with ALL and 60 control subjects. Participants were treated according to the ALL 2000 study protocol. Toxicities were assessed and associations with genotypes were evaluated according to Common Toxicity Criteria (NCI-CTC).Results
Significant associations were observed among carriers and the mutated genotype C3435T (ABCB1), which had an incidence of infection (p?=?0.05). Although no correlations were found between liver toxicity and glucose abnormalities for patients carrying ABCB1 SNPs, risk factors for liver toxicity were elevated by a factor of three for patients carrying the SNP G2677T, OR 3.00 (1.034–8.702). The risk factor of glucose abnormality toxicity for the patients carring T129C were increased three times OR 3.06 (0.486–19.198).Conclusions
In terms of infection incidence, polymorphism C3435T may contribute to potential life-threatening infections during paediatric ALL therapy, through glucocorticoid usage. 相似文献Objective
Acute mesenteric ischemia (AMI) is an emergent event with a high mortality rate; survivors have high rates of intestinal failure. Restoration of blood flow using endovascular or surgical revascularization is associated with better outcome in terms of survival rate and intestinal resection. Retrograde open mesenteric stenting (ROMS), which is a hybrid technique, combines two benefits: prompt blood flow restoration with an endovascular approach and inspection and resection of the small bowel. The aim of the study was to assess the results of ROMS in thrombotic AMI in a retrospective multicenter study.Methods
We retrospectively enrolled all consecutive patients who underwent ROMS revascularization for occlusive thrombotic AMI in three participating tertiary care centers between November 2012 and March 2017.Results
Twenty-five patients (14 men and 11 women; mean age, 64.9 ± 11.6 years) were included. In two patients, ROMS was not possible because of failure of re-entry in the aortic lumen (technical success, 92%). One patient required revascularization of two visceral arteries and underwent an aortohepatic bypass. Five patients (20%) underwent endarterectomy and patch angioplasty of the superior mesenteric artery before retrograde stenting. Thirteen patients (52%) required bowel or colon resection (11 patients required both resections) during the initial procedure with a mean length of small bowel resection of 52 ± 87 cm. The 30-day operative mortality rate was 25%, and the overall 1-year survival rate was 65%. The 1-year primary patency rate was 92%. In one patient, postoperative imaging at 1 month showed stent migration in the aortic bifurcation.Conclusions
ROMS for thrombotic AMI has a high technical success rate and a high midterm primary patency rate. It could be an alternative procedure to retrograde superior mesenteric artery bypass for patients when percutaneous endovascular revascularization is not indicated or has failed. 相似文献Methods: Fifty-four patients with ACI and 51 healthy controls were included in our study. Baseline characteristics and blood samples were collected for further analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the serum miR-124 levels. The dual-luciferase reporter assay was used to evaluate the effect of miR-124 on iASPP, a protein that inhibits apoptosis stimulating proteins in the p53 family.
Results: Compared with normal controls, the miR-124 levels in the ACI group rapidly decreased at phase 1 (within 24?h after ischemia) (p?<?0.001) and then gradually increased at phase 2 (48?~?72?h after ischemia) (p?<?0.001) and phase 3 (the 7th day after ischemia) (p?<?0.001). The dual-luciferase reporter assay showed that miR-124 down-regulates iASPP expression in 293T cells.
Conclusion: The miR-124 levels are down-regulated in ACI patients. The dynamic changes of miR-124 might provide a possible method for the detection of ischemic stroke.
- Highlights
The difference in miR-124 expression levels between ACI patients and normal controls.
Dynamic changes of miR-124 expression levels in ACI patients.
The down-regulation of miR-124 upon iASPP expression.
Methods:Nine APL patients received ATO (0.16 mg/kg/day) through 18-h infusion. Blood was collected before daily administration (days 2 to 9), and at different time points on day 8. Inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were detected by HPLC-ICP-MS.
Results:Arsenic species reached Cmax at 18 h on day 8. Arsenicals gradually accumulated during days 2 to 9, whereas their percentages remained almost constant. The general trend in red blood cells (RBCs) was iAs > MMA > DMA. MMA was consistently the predominant methylated arsenic metabolite in RBCs. iAs, MMA, and tAs (tAs = iAs + DMA + MMA) concentrations (P < 0.0001), MMA/DMA ratios (P = 0.0016) and iAs% (P = 0.0013) were higher in RBCs than in plasma.
Conclusions:Time course of arsenic species reveal kinetic characteristic of ATO metabolites in RBCs. Arsenic species accumulated with administration frequency. Arsenic species in RBCs were remarkably different from those in plasma. Time course of arsenic species in RBCs is important in ATO clinical application. 相似文献