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Yue Chen Deborah L Levy Summer Sheremata Philip S Holzman 《Neuropsychopharmacology》2004,55(8):834-841
BACKGROUND: Visual motion processing is compromised in schizophrenia, as shown in deficient velocity discrimination. Processing of motion signals comprises progressive stages along the geniculate-striate-extrastriate-cortex pathway. Based on neurophysiologic and brain lesion studies, a velocity discrimination deficit can implicate early-stage motion processing if it is contrast-dependent or late-stage motion processing if it is contrast-independent. METHODS: To determine which stage underlies the deficient velocity discrimination in schizophrenia, we examined the effects of visual contrast on velocity discrimination. We measured velocity discrimination thresholds in schizophrenia patients (n = 34) and normal control subjects (n = 17) at both low and high contrasts, using each subject's contrast detection threshold to equate contrast levels. RESULTS: Schizophrenia patients showed poor velocity discrimination that improved little with high contrast, whereas normal control subjects showed enhanced velocity discrimination with increased contrast. CONCLUSIONS: The finding that the velocity discrimination deficit in schizophrenia is independent of contrast modulation implicates the later, rather than the earlier, stages of motion processing, which is mediated in the extrastriate cortex. 相似文献
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Glucocorticoid receptor enhancement of pregnane X receptor-mediated CYP2B6 regulation in primary human hepatocytes. 总被引:2,自引:0,他引:2
Hongbing Wang Stephanie R Faucette Darryl Gilbert Summer L Jolley Tatsuya Sueyoshi Masahiko Negishi Edward L LeCluyse 《Drug metabolism and disposition》2003,31(5):620-630
Although the glucocorticoid receptor (GR) facilitates the xenobiotic-induced expression of CYP2B in rodents, its role in the regulation of human CYP2B6 is unclear. In this report, the role of human GR in the regulation of CYP2B6 was evaluated using primary human hepatocytes and transfection assays with Huh7 cells. CYP2B6 expression was not induced in primary hepatocytes treated with dexamethasone (DEX) concentrations (0.01-1 microM) known to activate GR. In contrast, treatment with 0.1 microM DEX enhanced CYP2B6 induction by different pregnane X receptor (PXR) activators, including rifampin, phenytoin, clotrimazole, and phenobarbital. In Huh7 cells, cotransfection of human (h)GR and hPXR with CYP2B6-phenobarbital-responsive enhancer module (PBREM) reporter constructs revealed that all hPXR ligands induce CYP2B6 reporter gene activity, and this ligand-dependent activation is greatly enhanced by activated hGR. CYP2B6 reporter gene expression was not induced in the presence of hPXR ligands when hGR alone was cotransfected with CYP2B6 reporter construct. In hGR and human constitutive androstane receptor (hCAR) cotransfection assays, activated hGR increased the constitutive activation of PBREM reporter constructs by hCAR in the absence of inducers. In the presence of activated hGR and known inducers of CYP2B6, only PB treatment caused a further 2-fold activation of hCAR compared with control. These studies show that hGR is involved synergistically in the xenobiotic-responsive regulation of human CYP2B6 by hPXR and hCAR. Moreover, the results suggest that the GR-enhanced expression of CYP2B6 is mediated through an indirect mechanism that does not require increased expression of nuclear receptor. 相似文献
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Responses of mitochondrial superoxide dismutase, catalase and glutathione peroxidase activities to aging 总被引:3,自引:0,他引:3
The previous observation (Eur. J. Biochem., 82 (1978) 563--567) that age-dependent accumulation of lipid peroxides follows as a consequence of increased radical formation in mitochondria has prompted an examination of the response of a set of protective enzymes to the above situation. Levels of mitochondrial catalase activity as well as selenium-dependent glutathione peroxidase activity were found to be increased with age, while superoxide dismutase activity remained unchanged. No selenium-independent glutathione peroxidase activity could be detected either in preparations from young 3-month-old controls or in preparations from 2-year-old rats. Both the relatively high and unchanged levels of reduced glutathione and kinetic considerations suggest that glutathione peroxidase is preferentially involved in lipid peroxide metabolism, while catalase predominantly metabolizes mitochondrial H2O2. 相似文献
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Véronique Douard Hye-In Choi Summer Elshenawy David Lagunoff Ronaldo P. Ferraris 《The Journal of physiology》2008,586(15):3657-3673
Fructose consumption has increased dramatically but little is known about mechanisms regulating the intestinal fructose transporter GLUT5 in vivo . In neonatal rats, GLUT5 can be induced only by luminal fructose and only after 14 days of age, unless the gut is primed with dexamethasone prior to fructose perfusion. To elucidate the mechanisms underlying dexamethasone modulation of GLUT5 development, we first identified the receptor mediating its effects then determined whether those effects were genomic. The glucocorticoid receptor (GR) antagonist RU486 dose-dependently prevented the dexamethasone-mediated effects on body weight, intestinal arginase2 (a known GR-regulated gene) and GLUT5. In contrast, an antagonist of the mineralocorticoid receptor as well as agonists of progesterone (PR) and pregnane-X (PXR) receptors did not block the effects of dexamethasone. These receptor antagonists and agonists had no effect on the intestinal glucose transporter SGLT1. Translocation of the GR into the enterocyte nucleus occurred only in dexamethasone-injected pups perfused with fructose, was accompanied by marked increases in brush border GLUT5 abundance, and was blocked by RU486. A priming duration of ∼24 h is optimal for induction but actinomycin D injection before dexamethasone priming prevented dexamethasone from allowing luminal fructose to induce GLUT5. Actinomycin D had no effect on dexamethasone-independent fructose-induced increases in glucose-6-phosphatase mRNA abundance, suggesting that it did not prevent fructose-induction of GLUT5, but instead prevented dexamethasone-induced synthesis of an intermediate required by fructose for GLUT5 regulation. In suckling rats < 14 days old, developmental regulation of transporters may involve cross-talk between hormonal signals modulating intestinal maturation and nutrient signals regulating specific transporters. 相似文献
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The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease 总被引:10,自引:0,他引:10
Raines EW 《International journal of experimental pathology》2000,81(3):173-182
The extracellular matrix (ECM) of the normal artery wall is a collection of fibrous proteins and associated glycoproteins embedded in a hydrated ground substance of glycosaminoglycans and proteoglycans. These distinct molecules are organized into a highly ordered network that are closely associated with the vascular cells that produce them. In addition to providing the architectural framework for the artery wall that imparts mechanical support and viscoelasticity, the ECM can regulate the behaviour of vascular cells, including their ability to migrate, proliferate and survive injury. The composition of the ECM is different within intimal lesions of atherosclerosis, which are composed of monocytes and lymphocytes from the circulation and smooth muscle cells (SMC) that migrate from the media to the intima (Ross 1993, 1999), and these differences may contribute to the altered phenotype of vascular cells within lesions. This review will briefly outline the ECM changes observed in atherosclerosis and restenosis and the potential relationship of these changes to altered vascular cell functions. 相似文献
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Yusuf A Al-Rawithi S Raines D Frayha H Toonsi TA Al-Mohsen I E-Yazigi A 《Therapeutic drug monitoring》1999,21(6):647-652
The authors describe a simplified high-performance liquid chromatographic (HPLC) method for the determination of gentamicin sulfate (GEN) in microsamples of plasma using 9-fluorenylmethyl chloroformate (FMOC) as a derivatizing agent and neomycin sulfate as the internal standard (IS). The drug and IS were separated on a 4 microm (particle size), 8 x 100 mm Nova-Pak C18 radial compression cartridge using a mixture of 84.5% acetonitrile and 15.5% water at a flow rate of 2.5 mL/min. The compounds were detected fluorometrically in the effluent at excitation and emission wavelengths of 260 nm and 315 nm, respectively. Sample preparation was performed on 50 microL of plasma using a simple liquid-liquid extraction followed by a room-temperature derivatization procedure. No interference from any endogenous substance or concurrently used drug was observed, and the retention times of the IS and three major components of GEN were 12.4, 19.5, 23.6, and 27.6 min, respectively. The concentration of the GEN in plasma for the range of 0.2-20.0 microg/mL was linearly (r > .997) related to the peak height ratio of the sum of the three major GEN peaks to that of the IS, with CV value at 0.3, 7.5, and 15 microg/mL being <3.61%. A comparison of the results from this assay versus fluorescence polarization immunoassay (TDx) showed a close agreement between the two methods with r = 0.994. This assay is currently being used to monitor GEN and investigate its pharmacokinetics in pediatric patients. 相似文献