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排序方式: 共有370条查询结果,搜索用时 500 毫秒
71.
Minuesa G Huber-Ruano I Pastor-Anglada M Koepsell H Clotet B Martinez-Picado J 《Pharmacology & therapeutics》2011,132(3):268-279
Current treatment of human immunodeficiency virus-1 (HIV-1) infection is effective, although it does not permanently suppress viral replication in all patients. Viral persistence, drug toxicity, and antiretroviral resistance are challenging barriers to successful treatment of HIV-1 infection. It has become increasingly apparent that the balance between drug influx and efflux transporter activity plays a critical role in the overall disposition of anti-HIV drugs in both cells and tissues. Thus, drug transporters directly influence the appearance of drug resistance and toxicity, and could also be related to persistence of HIV-1. We review the role of drug uptake transporters from the solute carrier (SLC) superfamily, their relation with specific antiretroviral drug disposition, and their efficacy in the tissues that absorb, metabolize, and eliminate anti-HIV drugs. Recent studies focusing on the role of drug uptake transporters in immune cells, key sites in the action of antiviral therapy, are highlighted. 相似文献
72.
We investigated the effect of carnitine supplementation during vitamin C (ASC) deficiency by measuring the levels of ASC and carnitine in plasma and cardiac muscle cells (CMC), and histological analysis with electron microscopy. The levels of carnitine were significantly decreased in ASC-deficient rats in plasma and the heart than those in the control. In carnitine supplemented ASC-deficient rats, a significant increase of carnitine levels were observed in both plasma and heart. The number of lipid droplets significantly increased in the ASC-deficient rats compared to the control rats, but did not increase in carnitine supplemented rats. These results indicate that ASC deficiency causes a generalized mitochondrial abnormality and accumulation of lipid droplets in CMC as observed in carnitine deficiency, and supplementation of carnitine prevented these changes even in the presence of ASC deficiency. 相似文献
73.
F.S. Ezgü Y. Atalay A. Hasanoğlu K. Gücüyener G. Biberoğlu E. Koç 《Nutritional neuroscience》2013,16(5-6):351-356
AbstractNeonatal hypoxic encephalopathy is one of the major causes of permanent neurological sequel. This study was conducted to investigate serum total, free and acylcarnitine levels in asphyxiated newborns with or without encephalopathy. Serum total, free and acylcarnitine levels were investigated in 21 newborns with and seven asphyxiated newborns without signs of encephalopathy. The newborns with encephalopathy were further divided into grade 1, 2 and 3 encephalopathy groups. Serum total and acylcarnitine concentrations of the whole encephalopathy group were significantly lower than the non-encephalopathy group ( p =0.042 for both). Serum total and acylcarnitine concentrations of grade 3 encephalopathy group were significantly lower than the non-encephalopathy group ( p =0.014 and p =0.040, respectively). No significant differences were noticed for free carnitine levels. Total carnitine levels were positively correlated with birth weight and 10th minute apgar score, whereas acylcarnitine levels were found to correlate with cord blood pH and free carnitine levels with birth weight. Cord blood pH, and total carnitine levels were found to be the most significant determinants of the neurological outcome at one year of age. It was emphasized that carnitine deficiency could occur in severely affected asphyxiated newborns and it is related to the outcome at one year of age. 相似文献
74.
Context: Osthole may be a dual agonist of peroxisome proliferator-activated receptors (PPAR) α/γ and ameliorate the insulin resistance (IR), but its mechanisms are not yet understood completely.Objective: We investigated the effects of osthole on PPARα/γ-mediated target genes involved in glucose and lipid metabolism in liver, adipose tissue, and skeletal muscle in fatty liver and IR rats.Materials and methods: The rat model was established by orally feeding high-fat and high-sucrose emulsion for 9 weeks. The experimental rats were treated with osthole 5–10?mg/kg by gavage after feeding the emulsion for 6 weeks, and were sacrificed 4 weeks after administration.Results: After treatment with osthole 5–10?mg/kg for 4 weeks, the lipid levels in serum and liver were decreased by 37.9–67.2% and 31.4–38.5% for triglyceride, 33.1–47.5% and 28.5–31.2% for free fatty acid, respectively, the fasting blood glucose, fasting serum insulin, and homeostasis model assessment of IR were also decreased by 17.2–22.7%, 25.9–26.7%, and 37.5–42.8%, respectively. Osthole treatment might simultaneously decrease the sterol regulatory element binding protein-1c, diacylglycerol acyltransferase, and fatty acid synthase mRNA expressions in liver and adipose tissue, and increase the carnitine palmitoyltransferase-1A mRNA expression in liver and glucose transporter-4 mRNA expression in skeletal muscle, especially in the osthole 10?mg/kg group (p?<?0.01).Discussion and conclusion: Osthole can improve glucose and lipid metabolism in fatty liver and IR rats, and its mechanisms may be associated with synergic modulation of PPARα/γ-mediated target genes involved in glucose and lipid metabolism in liver, adipose tissue, and skeletal muscle. 相似文献
75.
76.
S. Zierz R. R. Mundegar F. Jerusalem 《Journal of molecular medicine (Berlin, Germany)》1993,72(1):77-83
Summary Carnitine palmitoyltransferase (CPT) was studied in muscle homogenates of four patients with recurrent attacks of rhabdomyolysis due to muscular CPT deficiency and in those of the clinically asymptomatic father and mother of two patients. In controls CPT II was readily solubilized by the addition of Triton X-100 and 1% Tween 20. In contrast, CPT I was inactivated by Triton X-100 but remained catalytically active and membrane bound in the presence of 1% Tween 20. Total CPT activity was normal in patients and in both parents when measured under optimal assay conditions. After addition of 1% Tween 20 the insoluble CPT activity was also normal in patients and in both parents. The soluble CPT activity, however, was almost completely lost in patients but was only partially decreased in both parents. The data indicate that in patients an enzymatically active CPT II exists which is abnormally sensitive to inhibition by Tween 20, and that CPT I activity is not compensatorily increased in patients. A partial CPT II deficiency can be identified in heterozygotes most sensitively by the separate determination of soluble and insoluble CPT activities in the presence of 1% Tween 20.Abbreviations CoA
coenzyme A
- CPT
carnitine palmitoyltransferase 相似文献
77.
F. Proulx J. Lacroix I. A. Qureshi D. Nadeau M. Gauthier M. Lambert 《European journal of pediatrics》1997,156(11):864-869
In order to characterize the role of carnitine during metabolic stress, we prospectively determined carnitine profiles in
plasma and urine on admission, days 2, 5, 10 and 15, among 28 critically ill children free of any known conditions associated
with secondary carnitine deficiency. More than 25% of plasma and 50% of urinary carnitine measurements were abnormal; 96%
(27/28) of patients displayed on at least one occasion an abnormal [<−2 SD or >+2 SD] carnitine value in plasma. Three children
had extremely low [<10 μmol/l] free carnitine (FC) levels in plasma. Plasma esterified and FC levels on admission were not
related to the risk of mortality [PRISM score], to muscle lysis [CK values], and to the caloric intake. Levels of FC and esterified
carnitine in plasma were unrelated to those measured in urine.
Conclusion Abnormal plasma and urine carnitine measurements are frequently found in critically ill children; the biological significance
of these perturbations remains unclear. Caution must be exercised before concluding that an abnormal carnitine value is indicative
of an underlying hereditary metabolic disorder in this population.
Received: 7 March 1996 / Accepted: 14 April 1997 相似文献
78.
79.
心肌损伤过程中心肌细胞内肉毒硷含量的变化 总被引:1,自引:0,他引:1
本文通过对大鼠心肌的实验性坏死测定心肌细胞中肉毒硷的含量,并通过补充肉毒硷观察对心肌损伤的影响。结果提示,心肌损伤过程中。心肌细胞中游离肉毒硷的含量明显下降(P<0.01),通过静脉补充肉毒硷能提高心肌细胞中游离肉毒硷的含量(P<0.01)和减轻心肌损伤的程度。 相似文献
80.
John D Lloyd-Still Catherine A Powers Hans U Wessel 《Acta paediatrica (Oslo, Norway : 1992)》1993,82(2):145-149
Acylcarnitine is low in cord blood in patients with cystic fibrosis, suggesting that fatty acid metabolism is disturbed in utcro. Carnitine metabolites (total, free, short- and long-chain acylcarnitine) were measured prospectively in 23 newly diagnosed infants with cystic fibrosis treated with a carnitine-containing, predigested formula for 6–12 months. Total ( p < 0.002), free ( p < 0.004), and long-chain (p < 0.001) plasma concentrations of carnitines were significantly less than controls (n = 48) at diagnosis. Total and free concentrations were corrected with nutritional management, whereas short-and long-chain acylcarnitines remained unchanged. By three years of age all plasma concentrations of carnitine metabolites were significantly less than controls despite a carnitine-containing diet. Urinary carnitine metabolites were increased at diagnosis and follow-up. The physiological significance of these observations in cystic fibrosis is unknown, but could be compatible with disturbed regulatory control with resultant increased utilization. 相似文献