收费全文 | 3325篇 |
免费 | 217篇 |
国内免费 | 18篇 |
耳鼻咽喉 | 11篇 |
儿科学 | 83篇 |
妇产科学 | 54篇 |
基础医学 | 383篇 |
口腔科学 | 175篇 |
临床医学 | 320篇 |
内科学 | 631篇 |
皮肤病学 | 126篇 |
神经病学 | 252篇 |
特种医学 | 90篇 |
外科学 | 441篇 |
综合类 | 60篇 |
预防医学 | 253篇 |
眼科学 | 202篇 |
药学 | 309篇 |
中国医学 | 31篇 |
肿瘤学 | 139篇 |
2024年 | 7篇 |
2023年 | 52篇 |
2022年 | 117篇 |
2021年 | 229篇 |
2020年 | 128篇 |
2019年 | 184篇 |
2018年 | 199篇 |
2017年 | 144篇 |
2016年 | 159篇 |
2015年 | 140篇 |
2014年 | 187篇 |
2013年 | 224篇 |
2012年 | 347篇 |
2011年 | 325篇 |
2010年 | 177篇 |
2009年 | 142篇 |
2008年 | 172篇 |
2007年 | 189篇 |
2006年 | 129篇 |
2005年 | 114篇 |
2004年 | 68篇 |
2003年 | 53篇 |
2002年 | 42篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 2篇 |
Background
Neuroinflammation and oxidative stress has been shown to be associated with the development of Parkinson disease (PD). In the present study, we investigated the effect of intraperitoneal (i.p.) administration of silymarin, on 6-OHDA-induced motor-impairment, brain lipid per-oxidation and cerebrospinal fluid (CSF) levels of inflammatory cytokine in the rats.Results
The results showed that silymarin is able to improve motor coordination significantly (p < 0.001) in a dose dependent manner. There was a significant (p < 0.001) increase in MDA levels of 6-OHDA-lesioned rats whereas; in silymarin (100, 200 and 300 mg/kg, i.p. for 5 days) pre-treated hemi-parkinsonian rats MDA levels was decreased markedly (p < 0.001). Furthermore the CSF levels of IL-1β was decreased (p < 0.001) in silymarin (100, 200 and 300 mg/kg) pre-treated rats up to the range of normal non-parkinsonian animals.Conclusion
We found that pre-treatment with silymarin could improve 6-OHDA-induced motor imbalance by attenuating brain lipid per-oxidation as well as CSF level of IL-1β as a pro-inflammatory cytokine. We suggest a potential prophylactic effect for silymarin in PD. However, further clinical trial studies should be carried out to prove this hypothesis. 相似文献Purpose
The aim of this study was to evaluate the effectiveness of oral n-acetyl cysteine, as a potential nephroprotective agent, in preventing and/or attenuating amphotericin B-induced electrolytes imbalances.Methods
During a one year period, patients were to receive conventional amphotericin b for any indication for at least one week and were randomly allocated to receive either placebo or 600 mg oral n-acetyl cysteine twice daily during the treatment course of amphotericin b. Demographic and clinical data of the study population were gathered. Different aspects of amphotericin b nephrotoxicity including decrease of glomerular filtration rate, hypokalemia, hypomagnesemia, renal magnesium and potassium wasting were assessed. Each patient was monitored for any adverse reaction to n-acetyl cysteine. Sixteen and 14 patients in the n-acetyl cysteine and placebo groups completed the study, 3incidences of hypokalemia (75 % versus 70 %; P?=?0.724) and hypomagnesemia (30 % versus 20 %; P?=?0.468) did not differ significantly between placebo and NAC groups, respectively. Although the rate of AmB nephrotoxicity was higher in the placebo than in the NAC group (60 % versus 40 %), this difference was not statistically significant (P?=?0.209) even after adjusting for probable associated factors of amphotericin b nephrotoxicity (P?=?0.206). The incidence as well as time of onset of electrolyte abnormalities also did not differ significantly between placebo and n-acetyl cysteine groups. About 44 % of n-acetyl cysteine recipients experienced new onset nausea and a mild unpleasant taste during the study.Conclusion
Oral n-acetyl cysteine during the amphotericin B treatment course was not significantly effective in preventing or mitigating different features of its nephrotoxicity including decrease of glomerular filtration rate, hypokalemia, hypomagnesemia, and renal potassium as well as magnesium wasting. 相似文献Objectives
Plasmid-mediated AmpC β-lactamases (PMABLs) and carbapenemases are emerging groups of antimicrobial-resistance determinants. The aims of the study were to evaluate the occurrence of PMABLs and carbapenemases in clinical isolates of Klebsiella pneumoniae and compare the test performance of various phenotypic methods for detection of these enzymes in Iran.Methods
A total of 100 K. pneumoniae isolates were collected from clinical specimens obtained in Valiasr Hospital. AmpC production in all isolates was determined using the AmpC disk test, the cephamycin Hodge test, the AmpC Etest, and the boronic acid combined-disk test. In addition, carbapenemase production was determined using the modified Hodge test, the EDTA disk synergy test, and the boronic acid combined-disk test. The performances of various phenotypic methods were evaluated by the comparison of their results with polymerase chain reaction (PCR) method as the gold standard.Results
Of the 100 isolates, 19 (19%) were demonstrated to harbor the PMABL-resistance gene by the multiplex PCR method. The PCR result indicated the presence of carbapenemase genes in 12 isolates. The performance of various phenotypic tests carried out for detection of carbapenemase-producing isolates varied widely, ranging in sensitivity from 30% to 100% and in specificity from 90.8% to 100%.Conclusion
This is the first report of MOX-type AmpC β-lactamase and blaGES in K. pneumoniae in Iran. A comparison of the phenotypic methods showed that a combination of cefoxitin plus boronic acid is optimal for detecting plasmid-mediated AmpC enzymes in K. pneumoniae, whereas the implementation of molecular methods is often complex, requires specially trained personnel, and is associated with higher costs. 相似文献Background and Purpose
The hippocampal cell line HT22 is an excellent model for studying the consequences of endogenous oxidative stress. Extracellular glutamate depletes cellular glutathione by blocking the glutamate/cystine antiporter system xc−. Glutathione depletion induces a well-defined programme of cell death characterized by an increase in reactive oxygen species and mitochondrial dysfunction.Experimental Approach
We compared the mitochondrial shape, the abundance of mitochondrial complexes and the mitochondrial respiration of HT22 cells, selected based on their resistance to glutamate, with those of the glutamate-sensitive parental cell line.Key Results
Glutamate-resistant mitochondria were less fragmented and displayed seemingly contradictory features: mitochondrial calcium and superoxide were increased while high-resolution respirometry suggested a reduction in mitochondrial respiration. This was interpreted as a reverse activity of the ATP synthase under oxidative stress, leading to hydrolysis of ATP to maintain or even elevate the mitochondrial membrane potential, suggesting these cells endure ineffective energy metabolism to protect their membrane potential. Glutamate-resistant cells were also resistant to oligomycin, an inhibitor of the ATP synthase, but sensitive to deoxyglucose, an inhibitor of hexokinases. Exchanging glucose with galactose rendered resistant cells 1000-fold more sensitive to oligomycin. These results, together with a strong increase in cytosolic hexokinase 1 and 2, a reduced lactate production and an increased activity of glucose-6-phosphate dehydrogenase, suggest that glutamate-resistant HT22 cells shuttle most available glucose towards the hexose monophosphate shunt to increase glutathione recovery.Conclusions and Implications
These results indicate that mitochondrial and metabolic adaptations play an important role in the resistance of cells to oxidative stress.Linked Articles
This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 相似文献To compare the predictive roles of qualitative (PI-RADSv2) and quantitative assessment (ADC metrics), in differentiating Gleason pattern (GP) 3 + 4 from the more aggressive GP 4 + 3 prostate cancer (PCa) using radical prostatectomy (RP) specimen as the reference standard.
MethodsWe retrospectively identified treatment-naïve peripheral (PZ) and transitional zone (TZ) Gleason Score 7 PCa patients who underwent multiparametric 3T prostate MRI (DWI with b value of 0,1400 and where unavailable, 0,500) and subsequent RP from 2011 to 2015. For each lesion identified on MRI, a PI-RADSv2 score was assigned by a radiologist blinded to pathology data. A PI-RADSv2 score ≤ 3 was defined as “low risk,” a PI-RADSv2 score ≥ 4 as “high risk” for clinically significant PCa. Mean tumor ADC (ADCT), ADC of adjacent normal tissue (ADCN), and ADCratio (ADCT/ADCN) were calculated. Stepwise regression analysis using tumor location, ADCT and ADCratio, b value, low vs. high PI-RADSv2 score was performed to differentiate GP 3 + 4 from 4 + 3.
Results119 out of 645 cases initially identified met eligibility requirements. 76 lesions were GP 3 + 4, 43 were 4 + 3. ADCratio was significantly different between the two GP groups (p = 0.001). PI-RADSv2 score (“low” vs. “high”) was not significantly different between the two GP groups (p = 0.17). Regression analysis selected ADCT (p = 0.03) and ADCratio (p = 0.0007) as best predictors to differentiate GP 4 + 3 from 3 + 4. Estimated sensitivity, specificity, and accuracy of the predictive model in differentiating GP 4 + 3 from 3 + 4 were 37, 82, and 66%, respectively.
ConclusionsADC metrics could differentiate GP 3 + 4 from 4 + 3 PCa with high specificity and moderate accuracy while PI-RADSv2, did not differentiate between these patterns.
相似文献