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排序方式: 共有179条查询结果,搜索用时 15 毫秒
51.
52.
Josien C. Regelink Monique C. Minnema Evangelos Terpos Marjolein H. Kamphuis Pieter G. Raijmakers Indra C. Pieters – van den Bos Ben G. F. Heggelman Rutger‐Jan Nievelstein Rene. H. J. Otten Danielle van Lammeren – Venema Josee M. Zijlstra Anne I. J. Arens Jacky W. de Rooy Otto S. Hoekstra Reinier Raymakers Pieter Sonneveld Raymond W. Ostelo Sonja Zweegman 《British journal of haematology》2013,162(1):50-61
53.
18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor 总被引:3,自引:0,他引:3
Burns HD Van Laere K Sanabria-Bohórquez S Hamill TG Bormans G Eng WS Gibson R Ryan C Connolly B Patel S Krause S Vanko A Van Hecken A Dupont P De Lepeleire I Rothenberg P Stoch SA Cote J Hagmann WK Jewell JP Lin LS Liu P Goulet MT Gottesdiener K Wagner JA de Hoon J Mortelmans L Fong TM Hargreaves RJ 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(23):9800-9805
[(18)F]MK-9470 is a selective, high-affinity, inverse agonist (human IC(50), 0.7 nM) for the cannabinoid CB1 receptor (CB1R) that has been developed for use in human brain imaging. Autoradiographic studies in rhesus monkey brain showed that [(18)F]MK-9470 binding is aligned with the reported distribution of CB1 receptors with high specific binding in the cerebral cortex, cerebellum, caudate/putamen, globus pallidus, substantia nigra, and hippocampus. Positron emission tomography (PET) imaging studies in rhesus monkeys showed high brain uptake and a distribution pattern generally consistent with that seen in the autoradiographic studies. Uptake was blocked by pretreatment with a potent CB1 inverse agonist, MK-0364. The ratio of total to nonspecific binding in putamen was 4-5:1, indicative of a strong specific signal that was confirmed to be reversible via displacement studies with MK-0364. Baseline PET imaging studies in human research subject demonstrated behavior of [(18)F]MK-9470 very similar to that seen in monkeys, with very good test-retest variability (7%). Proof of concept studies in healthy young male human subjects showed that MK-0364, given orally, produced a dose-related reduction in [(18)F]MK-9470 binding reflecting CB1R receptor occupancy by the drug. Thus, [(18)F]MK-9470 has the potential to be a valuable, noninvasive research tool for the in vivo study of CB1R biology and pharmacology in a variety of neuropsychiatric disorders in humans. In addition, it allows demonstration of target engagement and noninvasive dose-occupancy studies to aid in dose selection for clinical trials of CB1R inverse agonists. 相似文献
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Ditor DS John SM Roy J Marx JC Kittmer C Weaver LC 《Journal of neuroscience research》2007,85(7):1458-1467
The purpose of this study was to determine the long-term effects of polyethylene glycol (PEG) and magnesium sulfate (MgSO(4)) on clinically relevant motor, sensory, and autonomic outcomes after spinal cord injury (SCI). Rats were injured by clip compression (50 g; T4) and treated 15 min and 6 hr postinjury intravenously (tail vein) with PEG (1 g/kg, 30% w/w in saline; n = 11), MgSO(4) (300 mg/kg; n = 5), PEG + MgSO(4) (n = 6), or saline (n = 10). Behavioral testing lasted for 6 weeks, followed by histological analysis of the spinal cord. Both PEG and MgSO(4) resulted in enhanced locomotor recovery and lower susceptibility to neuropathic pain (mechanical allodynia) compared with saline. At 6 weeks, BBB scores were 7.3 +/- 0.2, 7.7 +/- 0.4, and 6.4 +/- 0.6 in PEG-treated, MgSO(4)-treated, and saline-treated control groups, respectively. Likewise, at 6 weeks PEG-, MgSO(4)-, and saline-treated control animals showed 3.5 +/- 0.4, 2.8 +/- 0.9, and 5.0 +/- 0.5 avoidance responses to at-level touch, respectively. PEG + MgSO(4) improved locomotor recovery and reduced pain but did not provide additional benefit compared with either treatment alone. Neither treatment, nor their combination, attenuated mean arterial pressure (MAP) increases during autonomic dysreflexia. However, saline-treated controls had significantly lower resting MAP than PEG-treated rats and tended to have lower resting MAP than MgSO(4)-treated rats 6 weeks postinjury. MgSO(4) treatment and PEG + MgSO(4) treatment resulted in significant increases in dorsal myelin sparing, and the latter resulted in significant reductions in lesion volume, compared with saline-treated controls. Furthermore, mean lesion volumes correlated negatively with the corresponding mean BBB scores and positively with the corresponding mean pain scores. In conclusion, both PEG and MgSO(4) enhanced long-term clinical outcomes after SCI. 相似文献
56.
Koen Van Laere Michel Koole Sandra M Sanabria Bohorquez Karolien Goffin Ilonka Guenther Marie J Belanger Josee Cote Paul Rothenberg Inge De Lepeleire Igor D Grachev Richard J Hargreaves Guy Bormans H Donald Burns 《Journal of nuclear medicine》2008,49(3):439-445
The cannabinoid type-1 (CB1) receptor is one of the most abundant G-coupled protein receptors in the human body and is responsible for signal transduction of both endogenous and exogenous cannabinoids. The endocannabinoid system is strongly implicated in regulation of homeostasis and several neuropsychiatric disorders, obesity, and associated comorbidities, such as dyslipidemia and metabolic syndrome. We have used whole-body PET/CT to characterize the biodistribution and dosimetry of a novel high-affinity, subtype-selective radioligand, (18)F-MK-9470, in healthy male and female subjects. METHODS: Eight nonobese subjects (5 men, 3 women; age, 22-54 y) underwent serial whole-body PET/CT for 6 h after a bolus injection of 251 +/- 25 MBq (18)F-MK-9470 (N-[2-(3-cyano-phenyl)-3-(4-(2-(18)F-fluorethoxy)phenyl)-1-methylpropyl]-2-(5-methyl-2-pyridyloxy)-2-methylproponamide). Source organs were delineated 3-dimensionally using the combined morphologic and functional data. Residence times were derived from time-activity profiles using both the trapezoid rule and curve fitting. Individual organ doses and effective doses were determined using the OLINDA software package, with different approaches for gastrointestinal and urinary excretion modeling. RESULTS: (18)F-MK-9470 is taken up slowly in the brain, reaching a plateau at approximately 90-120 min after bolus injection and is excreted predominantly through the hepatobiliary system. The gallbladder, upper large intestine, small intestine, and liver are the organs with the highest absorbed dose (average: 159, 98, 87, and 86 microGy/MBq, respectively). The mean effective dose (ED) was 22.8 +/- 4.3 microSv/MBq, indicating relatively low intersubject variability and a mean value in the range of many commercially available (18)F-labeled radiopharmaceuticals. Brain uptake was relatively high compared with that of existing central nervous system ligands for other receptors, between 3.2% and 4.9% of the injected dose. CONCLUSION: The estimated radiation burden of (18)F-MK-9470 for PET CB1 receptor imaging shows relatively low variability between subjects and has an acceptable ED, which allows multiple serial cerebral scans of good image quality, while remaining within the risk category class II-b defined by the World Health Organization and the International Commission for Radiation Protection for a standard injected activity (185-370 MBq). 相似文献
57.
Heritability of blood pressure traits and the genetic contribution to blood pressure variance explained by four blood-pressure-related genes 总被引:3,自引:0,他引:3
van Rijn MJ Schut AF Aulchenko YS Deinum J Sayed-Tabatabaei FA Yazdanpanah M Isaacs A Axenovich TI Zorkoltseva IV Zillikens MC Pols HA Witteman JC Oostra BA van Duijn CM 《Journal of hypertension》2007,25(3):565-570
OBJECTIVE: To study the heritability of four blood pressure traits and the proportion of variance explained by four blood-pressure-related genes. METHODS: All participants are members of an extended pedigree from a Dutch genetically isolated population. Heritability and genetic correlations of systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure were assessed using a variance components approach (SOLAR). Polymorphisms of the alpha-adducin (ADD1), angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R) and G protein beta3 (GNB3) genes were typed. RESULTS: Heritability estimates were significant for all four blood pressure traits, ranging between 0.24 and 0.37. Genetic correlations between systolic blood pressure, diastolic blood pressure and mean arterial pressure were high (0.93-0.98), and those between pulse pressure and diastolic blood pressure were low (0.05). The ADD1 polymorphism explained 0.3% of the variance of pulse pressure (P = 0.07), and the polymorphism of GNB3 explained 0.4% of the variance of systolic blood pressure (P = 0.02), 0.2% of mean arterial pressure (P = 0.05) and 0.3% of pulse pressure (P = 0.06). CONCLUSION: Genetic factors contribute to a substantial proportion of blood pressure variance. In this study, the effect of polymorphisms of ADD1, AGT, AT1R and GNB3 explained a very small proportion of the heritability of blood pressure traits. As new genes associated with blood pressure are localized in the future, their effect on blood pressure variance should be calculated. 相似文献
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59.
Denis Monard 《Trends in neurosciences》1988,11(12):541-544
Proteolytic enzymes are localized at the growth cone where they are believed to sustain the motility and the penetration of the tip of the growing neurite. A glia derived neurite-promoting factor has been characterized as a potent protease inhibitor. These results seem at first glance paradoxical. However, they suggest that a delicate balance between cell-derived proteases and protease inhibitors modulates neurite elongation and regeneration. 相似文献
60.
Donna L. Johnston Daniel Keene Maria Kostova Lucie Lafay-Cousin Chris Fryer Katrin Scheinemann Anne-Sophie Carret Adam Fleming Vanessa Percy Samina Afzal Beverly Wilson Lynette Bowes Shayna Zelcer Chris Mpofu Mariana Silva Valerie Larouche Josee Brossard Douglas Strother Eric Bouffet 《Journal of neuro-oncology》2015,124(2):247-253