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131.
Enza Lacivita Paola De Giorgio Daniela Patarnello Mauro Niso Nicola A. Colabufo Francesco Berardi Roberto Perrone Grzegorz Satala Beata Duszynska Andrzej J. Bojarski Marcello Leopoldo 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2013,230(4):569-582
Serotonin 7 (5-hydroxytryptamine7 or 5-HT7) is the most recently identified serotonin receptor. It is involved in mood disorders and is studied as a target for antidepressants. Here, we report on the structural manipulation of the 5-HT7 receptor ligand 4-[2-(3-methoxyphenyl)ethyl]-1-(2-methoxyphenyl)piperazine (1a) aimed at obtaining 5-HT7 receptor ligands endowed with good in vitro metabolic stability. A set of N-[3-methoxyphenyl)ethyl-substituted] 1-arylpiperazine, 4-arylpiperidine and 1-aryl-4-aminopiperidine was synthesized and tested in radioligand binding assays at human cloned 5-HT7 and 5-HT1A receptors. In vitro metabolic stability of the target compounds was assessed after incubation with rat hepatic S9 microsomal fraction. Among the new compounds, 1-(2-biphenyl)-4-[2-(3-methoxyphenyl)ethyl]piperazine (1d) and 4-(2-biphenyl)-1-[2-(3-methoxyphenyl)ethyl]piperidine (2d) showed a good compromise between affinity at 5-HT7 receptor (K i = 7.5 nM and 13 nM, respectively) and in vitro metabolic stability (26 and 65 % recovery of parent compound, respectively) but were poorly selective over 5-HT1A receptor. 相似文献
132.
133.
Jakubczak Andrzej Kowalczyk Marek Mazurkiewicz Ilona Kondracki Marcin 《Virus genes》2021,57(3):258-265
Virus Genes - Mink astrovirus infection remains a poorly understood disease entity, and the aetiological agent itself causes disease with a heterogeneous course, including gastrointestinal and... 相似文献
134.
Beata Bobrowska Wojciech Zasada Andrzej Surdacki Tomasz Rakowski Pawe? Kleczyński Jolanta ?wierszcz Olga Kruszelnicka Renata Rajtar-Salwa Saleh Arif Danuta Sorysz Dariusz Dudek Jacek S. Dubiel 《International journal of medical sciences》2013,10(10):1361-1366
Background. Patients with degenerative aortic stenosis (AS) exhibit elevated prevalence of coronary artery disease (CAD) and internal carotid artery stenosis (ICAS). Our aim was to investigate prevalence of significant CAD and ICAS in relation to demographic and cardiovascular risk profile among patients with severe degenerative AS.Methods. We studied 145 consecutive patients (77 men and 68 women) aged 49-91 years (median, 76) with severe degenerative AS who underwent coronary angiography and carotid ultrasonography in our tertiary care center. The patients were divided into two groups according to the presence of either significant CAD (n=86) or ICAS (n=22).Results. The prevalence of significant CAD or ICAS was higher with increasing number of traditional risk factors (hypertension, hypercholesterolemia, diabetes, smoking habit) and decreasing renal function. We found interactions between age and gender in terms of CAD (p=0.01) and ICAS (p=0.06), which was confirmed by multivariate approach. With the reference to men with a below-median age, the prevalence of CAD or ICAS increased in men aged >76 years (89% vs. 55% and 28% vs. 14%, respectively), whereas the respective percentages were lower in older vs. younger women (48% vs. 54% and 7% vs. 17%).Conclusions. In severe degenerative AS gender modulates the association of age with coronary and carotid atherosclerosis with its lower prevalence in women aged >76 years compared to their younger counterparts. This may result from a hypothetical “survival bias”, i.e., an excessive risk of death in very elderly women with severe AS and coexisting relevant coronary or carotid atherosclerosis. 相似文献
135.
136.
Phosphate Kinetics During Weekly Cycle of Hemodialysis Sessions: Application of Mathematical Modeling
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Malgorzata Debowska Jan Poleszczuk Alicja Wojcik‐Zaluska Andrzej Ksiazek Wojciech Zaluska 《Artificial organs》2015,39(12):1005-1014
Both hyperphosphatemia and hypophosphatemia are associated with increased morbidity and mortality among patients on dialysis. The control of serum phosphate concentration is a considerable clinical problem. Our study aimed to improve understanding of phosphate kinetics in patients on dialysis using mathematical modeling. Three consecutive hemodialysis sessions with breaks of 2–2–3 days were monitored in 25 patients. Phosphate concentration was measured every hour and 45 min after the end of dialysis in blood serum and every 30 min in dialysate during each session. Volume of fluid compartments and body composition were assessed by bioimpedance. The pseudo one‐compartment model was applied to describe the profile of phosphate in blood serum during intra‐ and interdialytic periods of 1‐week cycle of three hemodialysis sessions. Model parameters, such as phosphate internal clearance (KM) and the rate of phosphate mobilization (RM), were correlated with the reduction of serum phosphate concentration during dialysis (Cpost/Cpre) and with equivalent continuous clearance (ECC) for phosphate. KM correlated negatively with predialysis serum phosphate concentration. There was significant positive correlation between RM and age. Postdialysis volume of phosphate central compartment was lower than, but correlated to, extracellular water volume. Parameters of the pseudo one‐compartment model, phosphate internal clearance, and the rate of phosphate inflow to the central compartment (the one accessible for dialysis) from other phosphate body reservoirs correlated with the indices of dialysis adequacy, such as reduction of serum phosphate and ECC. The pseudo one‐compartment model can be successfully extended from a single hemodialysis to the standard weekly cycle of sessions and the model parameters strongly correlate with the adequacy parameters of dialytic removal of phosphate. 相似文献
137.
Prof Fred Halter M.D. Adrian Schmassmann M.D. Andrzej Tarnawski M.D. 《Digestive diseases and sciences》1995,40(11):2481-2486
Grant support: Swiss National Science Foundation (grant 32-26478.89). 相似文献
138.
Szalay F Folhoffer A Horváth A Csak T Speer G Nagy Z Lakatos P Horváth C Habior A Tornai I Lakatos PL 《European journal of gastroenterology & hepatology》2005,17(9):923-928
BACKGROUND/AIM: The pathophysiology of osteoporosis in chronic liver diseases is unknown. Recent data suggest that serum leptin is associated with bone mineral density (BMD). In animal studies leptin was found to be a potent inhibitor of bone formation. We investigated the relationship between serum leptin levels, soluble leptin receptor (sOB-R), free leptin index (FLI) and BMD in patients with primary biliary cirrhosis (PBC). PATIENTS AND METHODS: Ninety-four female patients with PBC were included in this study; 122 healthy women served as controls. Serum leptin levels were measured by radioimmunoassay, sOB-R by enzyme-linked immunosorbent assay. BMD was measured by dual energy X-ray absorptiometry in the lumbar spine and femoral neck. RESULTS: Serum leptin was significantly lower in patients with PBC compared with healthy controls. No difference was found between the body mass index (BMI) of patients and controls. There was a strong positive correlation between leptin and BMI. In PBC no association was found between leptin, sOB-R and liver function tests, histological stages or the presence of osteoporosis. Osteoporosis was present in 38 patients. A positive correlation was found between serum leptin and femoral neck z-score even after adjustment for BMI, whereas serum sOB-R correlated inversely with the serum leptin level. There was no difference in FLI between the subgroups of PBC patients according to the stages of the disease. CONCLUSIONS: We found a lower serum leptin level and a higher sOB-R in patients with PBC, which could not be explained by the difference in BMI. As leptin was associated with BMD, it may be hypothesized that leptin is involved in the complex regulation of bone metabolism in PBC. 相似文献
139.
Olszówka P Domaradzki W Woś S Weglarzy A Jasiński M Szurlej D Zurek P Błach A 《Kardiologia polska》2003,59(11):428-430
A case of a 58-year-old female patient with unstable angina is presented. Two weeks earlier the patient suffered from acute myocardial infarction treated with thrombolysis. The patient underwent surgical revascularisation which was complicated by acute pulmonary embolism. Repeated surgery and inspection of pulmonary arteries revealed the presence of thrombus which was successfully removed. The post-operative course was uneventful. The causes and treatment of pulmonary embolism complicating coronary artery by-pass grafting are discussed. 相似文献
140.
Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF-alpha via the PI 3-kinase-Akt signaling pathway 总被引:4,自引:0,他引:4
Kawanaka H Jones MK Szabo IL Baatar D Pai R Tsugawa K Sugimachi K Sarfeh IJ Tarnawski AS 《Hepatology (Baltimore, Md.)》2002,35(2):393-402
Activation of endothelial nitric oxide synthase (eNOS) in portal hypertensive (PHT) gastric mucosa leads to hyperdynamic circulation and increased susceptibility to injury. However, the signaling mechanisms for eNOS activation in PHT gastric mucosa and the role of TNF-alpha in this signaling remain unknown. In PHT gastric mucosa we studied (1) eNOS phosphorylation (at serine 1177) required for its activation; (2) association of the phosphatidylinositol 3-kinase (PI 3-kinase), and its downstream effector Akt, with eNOS; and, (3) whether TNF-alpha neutralization affects eNOS phosphorylation and PI 3-kinase-Akt activation. To determine human relevance, we used human microvascular endothelial cells to examine directly whether TNF-alpha stimulates eNOS phosphorylation via PI 3-kinase. PHT gastric mucosa has significantly increased (1) eNOS phosphorylation at serine 1177 by 90% (P <.01); (2) membrane translocation (P <.05) and phosphorylation (P <.05) of p85 (regulatory subunit of PI 3-kinase) by 61% and 85%, respectively; (3) phosphorylation (P <.01) and activity (P <.01) of Akt by 40% and 52%, respectively; and (4) binding of Akt to eNOS by as much as 410% (P <.001). Neutralizing anti-TNF-alpha antibody significantly reduced p85 phosphorylation, phosphorylation and activity of Akt, and eNOS phosphorylation in PHT gastric mucosa to normal levels. Furthermore, TNF-alpha stimulated eNOS phosphorylation in human microvascular endothelial cells. In conclusion, these findings show that in PHT gastric mucosa, TNF-alpha stimulates eNOS phosphorylation at serine 1177 (required for its activation) via the PI 3-kinase-Akt signal transduction pathway. 相似文献