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Rajendran AJ Pandurangi UM Murali R Gomathi S Vijayan VK Cherian KM 《Indian heart journal》1998,50(5):531-534
The role of pre-operative short-term pulmonary rehabilitation in patients with chronic obstructive pulmonary disease who undergo coronary artery bypass graft surgery has been assessed for the first time prospectively. Forty-five patients posted for coronary artery bypass graft surgery were randomised to receive either short-term pulmonary rehabilitation (group I) or no such programme (group II). Patients of both the groups were evenly matched with respect to age, sex, body surface area, duration and severity of chronic obstructive pulmonary disease and coronary artery disease. Normal individuals who evenly matched with the study group were assessed for normal respiratory function parameters. Pre-operative and post-operative peak expiratory flow rate, inspiratory capacity, post-operative ventilation time, post-operative pulmonary complication and hospital stay were determined in both the groups. Peak expiratory flow rate (220.0 +/- 12.9 and 324.3 +/- 84.3 in group I, 218.0 +/- 16.4 and 260.5 +/- 35.2 in group II) and inspiratory capacity (844.0 +/- 147.4 and 1100.0 +/- 158.1 in group I, 830.0 +/- 117.4 and 1090 +/- 137 in group II) were significantly lower before and after surgery respectively in both groups compared to normal values. Even though both groups showed a significant rise in post-operative peak expiratory flow rate and inspiratory capacity after surgery, the post-operative peak expiratory flow rate and inspiratory capacity in group I was significantly higher than in group II. In group I, the post-operative ventilation time (24.5 +/- 6.00 hours), post-operative complications (n = 4) and hospital stay (12.4 +/- 3.6 days) were significantly lower than in group II (35.2 +/- 22.3 hours, n = 11, 18.8 +/- 6.6 days respectively). These data suggest that short-term pulmonary rehabilitation is feasible and effective in improving pulmonary functions before and after surgery and in reducing surgical morbidity and cost of medical care significantly. 相似文献
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Aswathy R Devan Keechilat Pavithran Bhagyalakshmi Nair Maneesha Murali Lekshmi R Nath 《World journal of gastroenterology : WJG》2022,28(36):5250-5264
Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that performs a dual role as a tumor suppressor and tumor promoter during cancer progression. Among different ligands of the TGF-β family, TGF-β1 modulates most of its biological outcomes. Despite the abundant expression of TGF-β1 in the liver, steatosis to hepatocellular carcinoma (HCC) progression triggers elevated TGF-β1 levels, contributing to poor prognosis and survival. Additionally, elevated TGF-β1 levels in the tumor microenvironment create an immunosuppressive stage via various mechanisms. TGF-β1 has a prime role as a diagnostic and prognostic biomarker in HCC. Moreover, TGF-β1 is widely studied as a therapeutic target either as monotherapy or combined with immune checkpoint inhibitors. This review provides clinical relevance and up-to-date information regarding the potential of TGF-β1 in diagnosis, prognosis, and therapy against HCC. 相似文献
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Intermittent outpatient ultrafiltration for the treatment of severe refractory congestive heart failure 总被引:2,自引:0,他引:2
Sheppard R Panyon J Pohwani AL Kapoor A Macgowan G McNamara D Mathier M Johnston JR Murali S 《Journal of cardiac failure》2004,10(5):380-383
BACKGROUND: Patients with severe congestive heart failure (CHF) become refractory to conventional medical therapy, leading to recurrent rehospitalizations. We examined the impact of intermittent outpatient ultrafiltration (UF), using either peritoneal dialysis or hemofiltration, on long-term clinical outcomes in patients with refractory CHF. METHODS AND RESULTS: We analyzed clinical and hemodynamic data in 19 consecutive patients with refractory CHF who received intermittent outpatient UF for at least 1 year between July 1998 and November 2002. The mean left ventricular ejection fraction of all 19 patients was 30.2 +/- 19.0%. All patients (100.0%) were New York Heart Association (NYHA) class IV. Only 5 patients (26.3%) received peritoneal dialysis; the remaining 14 (73.7%) received hemofiltration. There were 6 patients with a normal left ventricular ejection fraction (45%). After UF was started, the number of patients that were considered inotrope-dependent was reduced from 86.4% to 36.8% (P < .005). Compared with the year before UF was initiated, the number of CHF hospitalizations during follow-up was reduced from 2.6 to 0.3 (P < .005), and the NYHA class was improved from 4 to 3.1 (P < .005). Among all patients, 2 deaths were related to complications of UF, and cumulative 1-year survival was 63.2%. CONCLUSION: Our study suggests that UF is a safe, feasible therapy, but it needs further evaluation in carefully designed, prospective, randomized clinical trials. UF has the potential for offering another important therapeutic option for patients with severe and refractory CHF. 相似文献
46.
Crystal structure of Taq DNA polymerase in complex with an inhibitory Fab: The Fab is directed against an intermediate in the helix-coil dynamics of the enzyme 总被引:1,自引:0,他引:1
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R. Murali D. J. Sharkey J. L. Daiss H. M. Krishna Murthy 《Proceedings of the National Academy of Sciences of the United States of America》1998,95(21):12562-12567
We report the crystal structure of Thermus aquaticus DNA polymerase I in complex with an inhibitory Fab, TP7, directed against the native enzyme. Some of the residues present in a helical conformation in the native enzyme have adopted a γ turn conformation in the complex. Taken together, structural information that describes alteration of helical structure and solution studies that demonstrate the ability of TP7 to inhibit 100% of the polymerase activity of the enzyme suggest that the change in conformation is probably caused by trapping of an intermediate in the helix-coil dynamics of this helix by the Fab. Antibodies directed against modified helices in proteins have long been anticipated. The present structure provides direct crystallographic evidence. The Fab binds within the DNA binding cleft of the polymerase domain, interacting with several residues that are used by the enzyme in binding the primer:template complex. This result unequivocally corroborates inferences drawn from binding experiments and modeling calculations that the inhibitory activity of this Fab is directly attributable to its interference with DNA binding by the polymerase domain of the enzyme. The combination of interactions made by the Fab residues in both the polymerase and the vestigial editing nuclease domain of the enzyme reveal the structural basis of its preference for binding to DNA polymerases of the Thermus species. The orientation of the structure-specific nuclease domain with respect to the polymerase domain is significantly different from that seen in other structures of this polymerase. This reorientation does not appear to be antibody-induced and implies remarkably high relative mobility between these two domains. 相似文献
47.
Narasimha K Rao Vijayashankar Nataraj Mohan Ravi Love Panchariya Kirttija Palai Sumalatha R. Talapati Anirudha Lakshminarasimhan Murali Ramachandra Thomas Antony 《Chemical biology & drug design》2020,96(2):704-713
Acinetobacter baumannii is an opportunistic Gram‐negative bacterial pathogen, associated mostly with hospital‐acquired infections. The emergence of drug resistance strains made it necessary to explore new pathways for the development of more effective antibiotics. Enoyl CoA reductase (FabI), a key enzyme in the fatty acid biosynthesis (FAS) pathway, has emerged as a potential target for antibacterial drug development. Earlier reports show that the lead SaFabI inhibitor AFN‐1252 can inhibit FabI from other organisms including Escherichia coli and Burkholderia pseudomallei, but with differential potency. In the present work, we show that AFN‐1252 is a moderate inhibitor of AbFabI with an IC50 of 216 nM. AFN‐1252 stabilized AbFabI with a 4.2°C increase in the melting temperature (Tm) and, interestingly, the stabilization effect was significantly increased in presence of the cofactor NADH (?Tm = 17°C), suggesting the formation of a ternary complex AbFabI: AFN‐1252: NADH. X‐ray crystallography studies of AbFabI co‐crystalized with AFN‐1252 and NADH confirmed the ternary complex formation. The critical interactions of AFN‐1252 with AbFabI and NADH identified from the co‐crystal structure may facilitate the design and development of new drugs against A. baumannii infections by targeting the FAS pathway. 相似文献
48.
Hirotaka Kanzaki Akashi Ohtaki Faisal K. Merchant Mark I. Greene Ramachandran Murali 《Experimental and molecular pathology》2013
Osteoprotegerin (OPG) is a soluble receptor expressed in the serum of patients with diabetes, arthritis and pancreatic cancer. While OPG has been considered a tumor survival factor for bone metastasizing breast and prostate cancers, the role of OPG in pancreatic cancer, which itself rarely metastasizes to bone, is not known. Pancreatic ductal adenocarcinoma (PDAC) cell lines were found to secrete OPG and the level of OPG production correlated with sensitivity to TRAIL-induced apoptosis. Silencing OPG sensitized cells to TRAIL-induced apoptosis. Interestingly, a positive correlation was noted between OPG production level and K-Ras mutation status. Earlier studies implicated K-Ras in conferring resistance to TRAIL-induced apoptosis in pancreatic cells and this study demonstrates that K-Ras mediated TRAIL resistance in pancreatic cancer cells occurs due to increased OPG production. Silencing K-Ras in pancreatic cancer cells decreased OPG levels and increased sensitivity to TRAIL-induced apoptosis. These observations indicate that OPG can play a role in both cell survival and in PDAC cell sensitivity to TRAIL-induced apoptosis, which may contribute to metastasis. Targeted inhibition of OPG binding to TRAIL may represent a therapeutic approach in the treatment of pancreatic cancer. 相似文献
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