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1.
As many as 60 patients with combined pathologies (chronic hepatitis (CH) and chronic non-calculous cholecystitis (CNCC)) were examined, and 20 healthy subjects were included in the control group. The efficacy of Essliver Forte for patients with chronic non-calculous cholecystitis combined with chronic hepatitises (both viral hepatitis and steatohepatitis) was assessed on the basis of clinical, biochemical and bacteriological criteria. Essliver Forte was found to improve the clinical and biochemical parameters of the functional liver condition, bile biochemical characteristics and intestinal microbiocenosis in patients with combined pathologies. The positive clinical effect is most evident for patients with chronic non-calculous cholecystitis and chronic steatohepatitis (both alcohol and non-alcohol). Essliver Forte can be recommended for treatment of patients with combined pathologies. 相似文献
2.
Iwar Klime Antonian Vraana Jaroslav Kune Elena eboUkovaA Zdena Dobe ovaa Pavel tolba Josef Zicha 《Blood pressure》1995,4(3):137-142
Hereditary hypertriglyceridemic rats (hHTg) were developed as a new genetic model for the study of relationships between blood pressure (BP) and metabolic abnormalities. This strain has been produced by selective inbreeding from Wistar rats according to the rise of plasma triglycerides induced by a high-sucrose diet. Though hHTg rats display hypertriglyceridemia, impaired glucose tolerrance, hyperinsulinemia, insulin resistance and increased BP even without nutritional stimuli, high sucrose feeding further aggravates these symptoms. High plasma triglycerides levels in hHTg rats seem to be a consequence of their hyperproduction. Impaired insulin action is responsible for the defective glucoregulation in this strain. The loss of insulin responsiveness might be due to a reduction in the number of glucose transporters. Highly significant relationships among plasma triglycerides, ouabain-resistant Na+ transport and BP were demonstrated in the hHTg rats. Segregating populations (F2 hybrids) should be used for genetic analysis of the primary role of lipid and/or ion transport abnormalities in the pathogenesis of this form of genetic hypertension. 相似文献
3.
A prominent group of soluble glycoproteins with a molecular weight of 30K-40K and pI 5.0-5.6 was detected in various parts of the goldfish brain as well as in the optic nerves. Since these proteins are readily liberated from the tissue, we have designated them exoglycoproteins (X-GPs). The X-GPs in the optic tectum were found to be labeled after intraocular injection of radioactive tracers, in a manner consistent with the labeling of proteins transported in the optic axons. However, the labeling of X-GPs was blocked by intracranial injection of a protein synthesis inhibitor, whereas the labeling of axonally transported proteins was unaffected. This shows that the X-GPs can be synthesized locally within the brain. Nevertheless, when protein synthesis in the retina was blocked, the labeling of the X-GPs in the tectum was prevented, like the labeling of axonally transported proteins. Thus precursors for the synthesis of X-GPs can be derived from materials transported in the optic axons. This synthesis can occur in nonneuronal cells, as indicated by the incorporation of labeled amino acid into X-GPs in optic nerves directly exposed to the label. The synthesis of X-GPs was increased in regenerating nerves, suggesting that these proteins may play a role in regeneration. Partial amino acid sequencing of the proteins showed that they are identical to the proteins previously identified as "ependymins," which have been implicated in neuronal plasticity. There are minor differences in amino acid sequence among some individual spots. 相似文献
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5.
Zhao Y Sukbuntherng J Antonian L 《Journal of pharmaceutical and biomedical analysis》2004,35(3):513-522
SU5416 is a selective inhibitor of vascular endothelial growth factor (VEGF) receptor, which plays a major role in vascular angiogenesis. SU5416 exists as the thermodynamically stable and pharmacologically active cis isomer (Z-isomer) in the solid state. In light-exposed solutions the unstable trans isomer (E-isomer) is formed. The E-isomer is unstable for synthesis and isolation and the analytical standard of the E-isomer is unavailable. A new, simple, fast and reliable LC/MS/MS method was developed to quantify both isomers simultaneously in rat plasma samples in order to support the study of disposition kinetics of Z- and E-SU5416. This method is sensitive (LOQ = 0.5 ng/ml), reproducible, and has a wide linear range (0.5-2500 ng/ml). 相似文献
6.
Zhao Y Yang CY Haznedar J Antonian L 《Journal of pharmaceutical and biomedical analysis》2001,25(5-6):821-832
SU5416, Z-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone, is a cytostatic substance in development as an anti-angiogenic agent. SU5416 has several phase I and phase II metabolites including SU9838, SU6595, SU6689, 5′-hydroxy glucuronide of SU5416 and 5′-acyl glucuronide of SU5416. In order to support the preclinical studies, a liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) method for simultaneous determination of SU5416 and its metabolites in rat and dog plasma was developed. This method is fast, simple, sensitive (LOQ=2.0 ng/ml), reproducible and has a wide linear range (2.0–5000 ng/ml for SU5416, 2.0–2000 ng/ml for SU6689 and 2.0–1000 ng/ml for SU9838 and SU6595). This method was applied to rat and dog plasma samples obtained from pharmacokinetic and toxicokinetic studies. 相似文献
7.
Lida Antonian Meir Shinitzky David Samuel Arnold S. Lippa 《Neuroscience and biobehavioral reviews》1987,11(4):399-413
AL721, which is a novel lipid mixture extracted from egg yolks, is believed to be a therapeutic pharmacologic agent. AL721 interacts with membranes of various types of cells with a common mode of action. AL721 modifies cellular membrane composition and fluidity through passive extraction and/or exchange of cholesterol. Physiologically diminished cell function due to rigidification of its membrane is reversible both in vitro and in vivo by AL721. Fluidization of aged membranes with AL721 has been shown to restore brain serotonin receptor function both in vitro and in vivo. AL721 can also successfully restore deficient immune responsiveness of lymphocytes to mitogen stimulation in aged subjects. Drug tolerance to morphine and ethanol develops upon elevation of the viscosity of neuronal cell membranes in order to counteract the fluidization effect of the drug. Treatment of rigidified cellular membranes with AL721 in vivo can markedly reduce withdrawal symptoms. The virucidal effect of AL721 on the human immunodeficiency virus is believed to operate by lowering of viral membrane cholesterol thus interfering with the binding of the viral antigen to the host cell. Non-toxicity of AL721 is clearly demonstrated in animal and human safety studies. 相似文献
8.
9.
A A Antonian M A Levinskikh N I Sukhova 《Kosmicheskaia biologiia i aviakosmicheskaia meditsina》1985,19(4):69-73
The growth, development and metabolism of a new form of green unicellular algae Closteriopsis acicularis were investigated from the point of view of their potential use in the biological life support system (BLSS). Their growth and biochemical characteristics were studied as a function of nitrogen supply. During the nitrogen-deficiency cultivation the growth rate remained unchanged, cell division and biomass increment was uncoupled, and carbohydrate formation was predominant. The content of carbohydrates increased at the expense of assimilable fractions, particularly starch. These data can be used in the selection of an optimum nitrogen level for the case of algal continuous cultivation, in the calculation of material flow charts, and in the development of diets that can be provided by a BLSS incorporating Closteriopsis acicularis. 相似文献
10.
Biotransformation of the anti-angiogenic compound SU5416. 总被引:4,自引:0,他引:4
L Antonian H Zhang C Yang G Wagner L K Shawver M Shet B Ogilvie A Madan A Parkinson 《Drug metabolism and disposition》2000,28(12):1505-1512
SU5416 [3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1, 3-dihydro-indol-2-one], an inhibitor of VEGF (vascular endothelial growth factor) receptor tyrosine kinase, Flk-1/KDR (fetal liver kinase 1/kinase insert domain-containing receptor), also known as VEGF receptor 2 (VEGFR2) is in advanced clinical trials for treatment of AIDS-related Kaposi's sarcoma and colorectal and nonsmall cell lung cancers. Since this chemical class has not been studied previously with therapeutic intent, the present study was designed to investigate the in vitro metabolism of SU5416 by mouse, rat, dog, monkey, and human liver microsomes and to identify the major metabolites of SU5416. An HPLC procedure was developed and validated to resolve and quantify SU5416 and its metabolites. To evaluate the in vitro metabolism of SU5416, pooled liver microsomes from mice, rats, dogs, monkeys, and humans were incubated with SU5416 (25 microM) in the presence of an NADPH-generating system. In the presence of NADPH, mouse, rat, dog, monkey, and human liver microsomes converted SU5416 to at least 12, 9, 9, 7, and 6 polar metabolites, respectively. Microsomal metabolism of SU5416 showed marked species differences in the levels of different metabolites formed. The overall rate of SU5416 metabolism by liver microsomes from the species examined followed the rank order: monkey > or = mouse approximately rat > dog > human. Two major metabolites of SU5416 were identified, a hydroxymethyl derivative of SU5416 (M12) and a carboxylic acid derivative of SU5416 (M6), by spectroscopic methods and comparison with authentic compounds. Both of these oxidative metabolites were further metabolized in vivo through glucuronidation. The metabolic fate of SU5416 in microsomes from various species as well as data from in vivo biotransformation in the rat are discussed. 相似文献