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91.
Regulation of tissue factor and inflammatory mediators by Egr-1 in a mouse endotoxemia model 总被引:8,自引:0,他引:8
In septic shock, tissue factor (TF) activates blood coagulation, and cytokines and chemokines orchestrate an inflammatory response. In this study, the role of Egr-1 in lipopolysaccharide (LPS) induction of TF and inflammatory mediators in vivo was evaluated using Egr-1(+/+) and Egr-1(-/-) mice. Administration of LPS transiently increased the steady-state levels of Egr-1 mRNA in the kidneys and lungs of Egr-1(+/+) mice with maximal induction at one hour. Egr-1 was expressed in epithelial cells in the kidneys and lungs in untreated and LPS-treated mice. LPS induction of monocyte chemoattractant protein mRNA in the kidneys and lungs of Egr-1(-/-) mice was not affected at 3 hours, but its expression was significantly reduced at 8 hours compared with the expression observed in Egr-1(+/+) mice. Similarly, LPS induction of TF mRNA expression in the kidneys and lungs at 8 hours was reduced in Egr-1(-/-) mice. However, Egr-1 deficiency did not affect plasma levels of tumor necrosis factor alpha in endotoxemic mice. Moreover, Egr-1(+/+) and Egr-1(-/-) mice exhibited similar survival times in a model of acute endotoxemia. These data indicate that Egr-1 does not contribute to the early inflammatory response in the kidneys and lungs or the early systemic inflammatory response in endotoxemic mice. However, Egr-1 does contribute to the sustained expression of inflammatory mediators and to the maximal expression of TF at 8 hours in the kidneys and lungs. 相似文献
92.
Clinical characteristics and outcomes of patients with and without diabetes in the Surgical Treatment for Ischemic Heart Failure (STICH) trial 下载免费PDF全文
Michael R. MacDonald Lilin She Torsten Doenst Philip F. Binkley Jean L. Rouleau Ru‐San Tan Kerry L. Lee Alan B. Miller George Sopko Dominika Szalewska Myron A. Waclawiw Rafal Dabrowski Serenella Castelvecchio Christopher Adlbrecht Robert E. Michler Jae K. Oh Eric J. Velazquez Mark C. Petrie 《European journal of heart failure》2015,17(7):725-734
93.
Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia 总被引:18,自引:4,他引:18 下载免费PDF全文
Pawlinski R Pedersen B Schabbauer G Tencati M Holscher T Boisvert W Andrade-Gordon P Frank RD Mackman N 《Blood》2004,103(4):1342-1347
Sepsis is associated with a systemic activation of coagulation and an excessive inflammatory response. Anticoagulants have been shown to inhibit both coagulation and inflammation in sepsis. In this study, we used both genetic and pharmacologic approaches to analyze the role of tissue factor and protease-activated receptors in coagulation and inflammation in a mouse endotoxemia model. We used mice expressing low levels of the procoagulant molecule, tissue factor (TF), to analyze the effects of TF deficiency either in all tissues or selectively in hematopoietic cells. Low TF mice had reduced coagulation, inflammation, and mortality compared with control mice. Similarly, a deficiency of TF expression by hematopoietic cells reduced lipopolysaccharide (LPS)-induced coagulation, inflammation, and mortality. Inhibition of the down-stream coagulation protease, thrombin, reduced fibrin deposition and prolonged survival without affecting inflammation. Deficiency of either protease activated receptor-1 (PAR-1) or protease activated receptor-2 (PAR-2) alone did not affect inflammation or survival. However, a combination of thrombin inhibition and PAR-2 deficiency reduced inflammation and mortality. These data demonstrate that hematopoietic cells are the major pathologic site of TF expression during endotoxemia and suggest that multiple protease-activated receptors mediate crosstalk between coagulation and inflammation. 相似文献
94.
Adam Antosik Kamila Czubak Arkadiusz Gajek Agnieszka Marczak Rafal Glowacki Kamila Borowczyk Halina Malgorzata Zbikowska 《Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie》2015,42(3):140-148
Background
To investigate the extent of oxidative damage and changes in morphology of manually isolated red blood cells (RBCs) from whole blood, cold stored (up to 20 days) in polystyrene tubes and subjected to pre-storage irradiation (50 Gy) and to compare the properties of SAGM-preserved RBCs stored under experimental conditions (polystyrene tubes) with RBCs from standard blood bag storage.Methods
The percentage of hemolysis as well as the extracellular activity of LDH, thiobarbituric acid-reactive substances, reduced glutathione (GSH), and total antioxidant capacity (TAC) were measured. Changes in the topology of RBC membrane, shape, and size were evaluated by flow cytometry and judged against microscopy images.Results
Irradiation caused significant LDH release as well as increased hemolysis and lipid peroxidation, GSH depletion, and reduction of TAC. Prolonged storage of irradiated RBCs resulted in phosphatidylserine exposure on the cell surface. By day 20, approximately 60% of RBCs displayed non-discoid shape. We did not notice significant differences in percentage of altered cells and cell volume between RBCs exposed to irradiation and those not exposed.Conclusion
Irradiation of RBC transfusion units with a dose of 50 Gy should be avoided. For research purposes such as studying the role of antioxidants, storage of small volumes of RBCs derived from the same donor would be more useful, cheaper, and blood-saving.Key Words: Red blood cell, Gamma irradiation, Storage, Oxygen-free radical, Flow cytometry 相似文献95.
96.
Cristina Jiménez-Ortigosa Padmaja Paderu Mary R. Motyl David S. Perlin 《Antimicrobial agents and chemotherapy》2014,58(2):1248-1251
MK-3118 is as an orally active new antifungal in the early stage of clinical development that inhibits the biosynthesis of β-(1,3)-glucan. We evaluated the in vitro activity of this compound against wild-type and echinocandin-resistant (ER) isolates containing mutations in the FKS gene(s) of Candida spp. and Aspergillus spp. MK-3118 demonstrated enhanced efficacy for most C. albicans and C. glabrata ER isolates relative to caspofungin, with decreased MICs and half-maximal inhibitory concentrations (IC50s). 相似文献
97.
Muhammed Z. Khawaja MBBS Manav Sohal MBBS Haseeb Valli MBBS Rafal Dworakowski PhD Stephen J. Pettit PhD David Roy MBBS James Newton MD Heiko Schneider MD Ganesh Manoharan MD Sagar Doshi MD Douglas Muir MD David Roberts MD James Nolan MD Mark Gunning MD Cameron Densem MD Mark S. Spence MD Saqib Chowdhary PhD Vaikom S. Mahadevan MD Stephen J. Brecker MD Philip MacCarthy PhD Michael Mullen MD Rodney H. Stables DM Bernard D. Prendergast DM Adam de Belder MD Martyn Thomas MD Simon Redwood MD David Hildick‐Smith MD 《Catheterization and cardiovascular interventions》2013,81(2):366-373
98.
Vandad Yousefi Rafal Maslowski 《Canadian family physician Médecin de famille canadien》2013,59(7):762-767
Objective
To identify the underlying systemic drivers of the development and ongoing expansion of hospitalist programs in Canada.Data sources
MEDLINE and Google Scholar were searched using combinations of the terms hospitalist, hospital medicine, and Canada.Study selection
All publications that addressed the study question, including review articles, original research, editorials, commentaries, and letters or news articles, were included in the review.Synthesis
Constant comparative methodology was used to analyze and code the articles and to synthesize the identified codes into broader themes. Three broad categories were identified: physician-related drivers, health system–related drivers, and patient-related drivers. Within each category, we identified a number of drivers.Conclusion
Many drivers have been cited in the literature as reasons behind the emergence and growth of the hospitalist model in the Canadian health care system. While their interplay makes simple cause-and-effect conclusions difficult, these drivers demonstrate that hospitalist programs in Canada have developed in response to a complex set of provider, system, and patient factors. 相似文献99.
Rafal Al-Saigh Maria Siopi Nikolaos Siafakas Aristea Velegraki Loukia Zerva Joseph Meletiadis 《Antimicrobial agents and chemotherapy》2013,57(8):3713-3718
Conventional MIC testing of amphotericin B results in narrow MIC ranges challenging the detection of resistant strains. In order to discern amphotericin B pharmacodynamics, the in vitro activity of amphotericin B was studied against Aspergillus isolates with the same MICs by using a new in vitro pharmacokinetic/pharmacodynamic (PK/PD) model that simulates amphotericin B human plasma levels. Clinical isolates of Aspergillus fumigatus, A. terreus, and A. flavus with the same Clinical and Laboratory Standards Institute modal MICs of 1 mg/liter were exposed to amphotericin B concentrations following the plasma concentration-time profile after single-bolus administration with Cmax values of 0.6, 1.2, 2.4, and 4.8 mg/liter. Fungal growth was monitored for up to 72 h based on galactomannan production. Complete growth inhibition was observed only against A. fumigatus with amphotericin B with a Cmax of ≥2.4 mg/liter. At the lower Cmax values 0.6 and 1.2 mg/liter, significant growth delays of 34 and 52 h were observed, respectively (P < 0.001). For A. flavus, there was no complete inhibition but a progressive growth delay of 1 to 50 h at an amphotericin B Cmax of 0.6 to 4.8 mg/liter (P < 0.001). For A. terreus, the growth delay was modest (up to 8 h) at all Cmaxs (P < 0.05). The Cmax (95% confidence interval) associated with 50% activity for A. fumigatus was 0.60 (0.49 to 0.72) mg/liter, which was significantly lower than for A. flavus 3.06 (2.46 to 3.80) mg/liter and for A. terreus 7.90 (5.20 to 12.29) mg/liter (P < 0.001). A differential in vitro activity of amphotericin B was found among Aspergillus species despite the same MIC in the order A. fumigatus > A. flavus > A. terreus in the in vitro PK/PD model, possibly reflecting the different concentration- and time-dependent inhibitory/killing activities amphotericin B exerted against these species. 相似文献