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571.
Franks PW Farooqi IS Luan J Wong MY Halsall I O'Rahilly S Wareham NJ 《The Journal of clinical endocrinology and metabolism》2003,88(7):3258-3263
Leptin is secreted by adipose tissue and acts upon receptors located in the hypothalamus to modify energy balance. Investigations of the relationship between leptin and physical activity energy expenditure (PAEE) at population level are scarce. The majority of studies addressing this topic are limited by their measurement of PAEE (i.e. questionnaires or ecological comparisons between rural and urban ethnic groups). To our knowledge, no studies have directly examined the relationship of objectively assessed PAEE and leptin in a large free-living population-based cohort. Therefore, we measured fasting plasma leptin and insulin concentrations, cardiorespiratory fitness (O(2max.pred)), PAEE, and body composition in 758 Caucasian people (aged 40-65 yr). In sex-combined multiple regression analyses, leptin was significantly associated with PAEE (beta = -0.19, P = 0.0027), but not with O(2max.pred) (beta = -0.0002, p = NS). The association between PAEE and leptin was significant in men when adjusted for percentage of body fat (beta = -0.28, P = 0.004) but not women (beta = -0.12, P = 0.18) but was significant in both men and women when adjusted for body mass index (men: beta = -0.28, P = 0.005; women: beta = -0.23, P = 0.01; combined: beta = -0.26, P = 0.00008). These data suggest the existence in this population of an independent inverse association between PAEE and fasting plasma leptin level. 相似文献
572.
Ali A Thompson CF Balkovec JM Graham DW Hammond ML Quraishi N Tata JR Einstein M Ge L Harris G Kelly TM Mazur P Pandit S Santoro J Sitlani A Wang C Williamson J Miller DK Thompson CM Zaller DM Forrest MJ Carballo-Jane E Luell S 《Journal of medicinal chemistry》2004,47(10):2441-2452
A novel series of selective ligands for the human glucocorticoid receptor (hGR) are described. Preliminary structure-activity relationships were focused on substitution at C-1 and indicated a preference for 3-, 4-, and 5-substituted aromatic and benzylic groups. The resulting analogues, e.g., 18 and 34, exhibited excellent affinity for hGR (IC(50) 1.9 nM and 2.8 nM, respectively) and an interesting partial agonist profile in functional assays of transactivation (tyrosine aminotransferase, TAT, and glutamine synthetase, GS) and transrepression (IL-6). The most potent compounds described in this study were the tertiary alcohol derivatives 21 and 25. These candidates showed highly efficacious IL-6 inhibition versus dexamethasone. The thiophenyl analogue 25 was evaluated in vivo in the mouse LPS challenge model and showed an ED(50) = 4.0 mg/kg, compared to 0.5 mg/kg for prednisolone in the same assay. 相似文献
573.
Basch E Boon H Davies-Heerema T Foppo I Hashmi S Hasskarl J Sollars D Ulbricht C 《Journal of herbal pharmacotherapy》2004,4(3):63-83
An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. 相似文献
574.
575.
Transgenic mice overexpressing human Bcl-2 are resistant to hepatic ischemia and reperfusion 总被引:17,自引:0,他引:17
Selzner M Rüdiger HA Selzner N Thomas DW Sindram D Clavien PA 《Journal of hepatology》2002,36(2):218-225
BACKGROUND/AIMS: Apoptosis is a key mechanism of reperfusion injury in the ischemic liver. The apoptotic pathway is highly regulated by anti-apoptotic factors, such as Bcl-2. We evaluated the effect of Bcl-2 overexpression on apoptosis and the activation of the apoptotic cascade after hepatic ischemia and reperfusion. METHODS: Ninety minutes of ischemia and reperfusion was performed in Bcl-2 transgenic and non-transgenic mice. Bcl-2 overexpression was determined by immunohistochemistry and Western blot. Liver injury was determined by aspartate aminotransferase (AST), Tunel test and the activation of the apoptotic cascade and animal survival. RESULTS: Bcl-2 overexpression was present in all hepatocytes and non-parenchymal liver cells in transgenic mice. Bcl-2 overexpression resulted in significant decreased AST levels after ischemic injury, and complete inhibition of apoptosis. After 90 min of total hepatic ischemia all control mice died, while four transgenic mice survived permanently. Bcl-2 overexpression was associated with inhibition of caspase 3 activation after reperfusion and increased baseline levels of cytoplasmic cytochrome c, caspase 3, and a reduction of Bcl-x(L) production. CONCLUSIONS: Bcl-2 overexpression protects against ischemic injury by inhibiting apoptosis. Extensive overproduction of Bcl-2 is associated with a compensatory increase of baseline levels of cytoplasmic cytochrome c and caspase 3, and a deletion of Bcl-x(L). 相似文献
576.
Tan WH Eichler FS Hoda S Lee MS Baris H Hanley CA Grant PE Krishnamoorthy KS Shih VE 《Pediatrics》2005,116(3):757-766
Isolated sulfite oxidase deficiency is a rare but devastating neurologic disease that usually presents in early infancy with seizures and alterations in muscle tone. Only 21 cases have been reported in the literature. We report a case of a newborn infant boy with isolated sulfite oxidase deficiency who presented with generalized seizures on his fourth day of life. Plasma total homocysteine was not detectable. Urinary sulfite, thiosulfate, and S-sulfocysteine levels were elevated. The patient began a low-methionine and low-cysteine diet and was treated with thiamine and dextromethorphan. However, he became increasingly microcephalic and was severely developmentally delayed. Mutation analysis of the sulfite oxidase gene revealed that the patient was homozygous for a novel 4-base pair deletion, and both of his parents were found to be heterozygous carriers of the same deletion. We reviewed the clinical, biochemical, neuroradiologic, and neuropathologic features in all published cases of isolated sulfite oxidase deficiency. Seizures or abnormal movements were prominent features in all cases. Developmental delays were reported in 17 cases. Ectopia lentis was detected in 9 cases. Clinical improvement with dietary therapy was seen in only 2 patients, both of whom presented after the age of 6 months and had relatively mild developmental delays. Plasma or urinary S-sulfocysteine levels were elevated in all cases. Urinary sulfite was detected in all except 1 case. Cerebral atrophy and cystic encephalomalacia were observed with neuroradiologic imaging and were noted in all 3 postmortem reports of isolated sulfite oxidase deficiency. The main alternative in the differential diagnosis of isolated sulfite oxidase deficiency is molybdenum cofactor deficiency. 相似文献
577.
578.
Levy MH Back A Bazargan S Benedetti C Billings JA Block S Bruera E Carducci MA Dy S Eberle C Foley KM Harris JD Knight SJ Milch R Rhiner M Slatkin NE Spiegel D Sutton L Urba S Von Roenn JH Weinstein SM;National Comprehensive Cancer Network 《Journal of the National Comprehensive Cancer Network : JNCCN》2006,4(8):776-818
579.
Ulbricht C Basch E Bent S Boon H Corrado M Foppa I Hashmi S Hammerness P Kingsbury E Smith M Szapary P Vora M Weissner W 《Journal of the Society for Integrative Oncology》2006,4(4):170-186
Here presented is an evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. 相似文献
580.
Bhattacharyya S Luan J Farooqi IS Keogh J Montague C Brennand J Jorde L Wareham NJ O'Rahilly S 《The Journal of endocrinology》2004,183(1):115-120
Central administration of neuromedin U (NMU) suppresses food intake acting through the NMU-2 receptor (NMU2R), which is expressed in the hypothalamus. We screened the NMU2R gene in 96 patients with severe early-onset obesity. A common variant haplotype was found (f-0.21). This common variant haplotype was unusual in nature, consisting of four non-contiguous missense changes in complete linkage disequilibrium, and across two separate exons. The variant haplotype resulted in four amino acid substitutions (S295T/F312L/P380L/ M385 V) and was present in several other Europid populations and in subjects of South Asian, East Asian and African American origin, but not in eleven African Pygmies. This variant haplotype was not associated with obesity or related traits in 500 subjects from a prospective population-based cohort. In summary, we have identified two markedly different isoforms of the NMU-2 receptor, presumably arising through an ancient and complex mutational event; no genetic associations between this haplotype and obesity-related traits were, however, discerned. Further investigation of the pharmacogenomic consequences of NMU2R variation in humans is warranted. 相似文献