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71.
To define the toxicity profile of recombinant human interleukin-6 (rhIL- 6) and to study its effect on hematopoiesis, biochemical parameters and other cytokines, rhIL-6 was administered in a phase I-II study to 20 patients with breast carcinoma or nonsmall cell lung cancer. RhIL-6 doses were 0.5, 1.0, 2.5, 5.0, 10, and 20 micrograms/kg/d, with at least three patients per dose level. RhIL-6 was administered 24 hours by continuous intravenous infusion followed by subcutaneous (SC) administration for 6 days, partly on an outpatient basis. RhIL-6- related side effects were fever, headache, myalgia, and local erythema. Starting at 2.5 micrograms/kg/d, these side effects were compounded by nausea, reversible increase in liver enzymes, and anemia. Flu-like symptoms were controllable up to and including 10 micrograms rhIL- 6/kg/d with acetaminophen. RhIL-6 increased platelet counts with a decrease in mean platelet volume and increased leukocytes caused by neutrophil, monocyte, and lymphocyte increase, with an increase in T cells and natural killer cells at 1.0 and 2.5 micrograms rhIL-6/kg/d. The reversible anemia was characterized by a decrease in serum iron, and an increase in ferritin and erythropoietin without reticulocytosis. RhIL-6 reduced total cholesterol levels and a dose-related increase of C-reactive protein and serum amyloid A plasma levels was observed. Serum IL-6 levels were increased, especially at 10 and 20 micrograms/kg/d, whereas no change in IL-1 beta and tumor necrosis factor alpha levels was observed. RhIL-6 can be administered with controllable side effects in this setting, up to and including a SC dose of 10 micrograms/kg/d on an outpatient basis, and has a promising stimulating effect on leukopoiesis and thrombopoiesis.  相似文献   
72.
Congenital heart disease: gated MR imaging in 72 patients   总被引:9,自引:0,他引:9  
Seventy-two patients (aged 2 months to 75 years; mean 23 years) with a variety of congenital anomalies of the heart and great vessels underwent ECG-gated magnetic resonance (MR) imaging using the multisectional spin-echo technique (0.35 Tesla). The ability to define segmental anatomy and intracardiac anomalies on transverse, sagittal, and coronal images was evaluated. MR images were graded as excellent, diagnostic, or nondiagnostic, and MR findings were corroborated by angiography and/or two-dimensional echocardiography. Studies that were considered to be excellent or diagnostic were obtained in 96% of the cases. Visceroatrial situs, the type of ventricular loop, and the relationship of the great vessels could be identified in all patients with studies encompassing the entire heart. Forty-four of 47 abnormalities at the level of the great vessels were identified with MR, including coarctation of the aorta and vascular rings. MR showed 32 of 35 ventricular abnormalities; 2 small ventricular septal defects and 1 Ebstein anomaly were not demonstrated. All of the abnormalities at the atrial level and those of systemic and pulmonary venous return were seen on MR images. Complex cardiac anomalies, such as single ventricles, and the status of the pulmonary arteries were clearly demonstrated, and a good assessment of total and palliative postoperative anatomy was provided.  相似文献   
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The relationship between the multimeric size of factor VIII-von Willebrand factor (FVIII-vWF) and the support of platelet adhesion to subendothelium was studied in an annular perfusion chamber, employing human renal and umbilical arteries. Commercial factor VIII concentrates containing multimers of low molecular weight that had been shown not to correct the bleeding time upon infusion into patients with von Willebrand's disease did not support platelet adhesion in the perfusion chamber. Cryoprecipitate and two experimental FVIII-vWF concentrates containing multimers of high molecular weight supported platelet adhesion. Factor VIII-vWF purified from cryoprecipitate was subdivided into three fractions of different molecular weights (6.0-14.0, 4.0-9.0, and 3.0-7.5 X 10(6) dalton). These fractions appeared to bind equally well and to be equally effective in supporting platelet adhesion. Factor VIII-vWF with multimers of low molecular weight (0.5-1.5 X 10(6) dalton) were prepared by partial reduction. Binding of FVIII-vWF to subendothelium was not impaired, and the support of platelet adhesion appeared to be more resistant to the effect of reduction than the ristocetin cofactor activity. At high shear rate (2,500 sec-1), increased platelet adhesion was observed with partially reduced FVIII- vWF. These data indicate that the ability of FVIII-vWF preparations to correct the bleeding time is reflected in enhanced platelet adhesion to subendothelium in a perfusion chamber. These data also emphasize that multimeric size is not the only factor determining whether FVIII-vWF will support platelet adhesion.  相似文献   
75.
Gordon  PB; Goldenberg  SL; Chan  NH 《Radiology》1993,189(2):573
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76.
The insulinotropic hormone glucagon-like peptide-1 (7-36)-amide (GLP-1) has potent effects on glucose-dependent insulin secretion, insulin gene expression, and pancreatic islet cell formation and is presently in clinical trials as a therapy for type 2 diabetes mellitus. We report on the effects of GLP-1 and two of its long-acting analogs, exendin-4 and exendin-4 WOT, on neuronal proliferation and differentiation, and on the metabolism of two neuronal proteins in the rat pheochromocytoma (PC12) cell line, which has been shown to express the GLP-1 receptor. We observed that GLP-1 and exendin-4 induced neurite outgrowth in a manner similar to nerve growth factor (NGF), which was reversed by coincubation with the selective GLP-1 receptor antagonist exendin (9-39). Furthermore, exendin-4 could promote NGF-initiated differentiation and may rescue degenerating cells after NGF-mediated withdrawal. These effects were induced in the absence of cellular dysfunction and toxicity as quantitatively measured by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays, respectively. Our findings suggest that such peptides may be used in reversing or halting the neurodegenerative process observed in neurodegenerative diseases, such as the peripheral neuropathy associated with type 2 diabetes mellitus and Alzheimer's and Parkinson's diseases. Due to its novel twin action, GLP-1 and exendin-4 have therapeutic potential for the treatment of diabetic peripheral neuropathy and these central nervous system disorders.  相似文献   
77.
Published reports and personal experience are reviewed relating to patients under 1 year of age diagnosed with a vein of Galen malformation and congenital heart disease. Including five patients from this institution, a total of 23 patients (12 neonates) with congenital heart disease and a vein of Galen malformation have been reported. Six of these had sinus venosus atrial septal defect and nine had aortic coarctation.  相似文献   
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The mechanisms underlying excessive menstrual bleeding or menorrhagia are not understood. In view of its potent vasoconstrictor and growth factor properties, endothelin has been proposed to have a potential paracrine role in the regulation of uterine blood flow and therefore could be a factor in menorrhagia. We compared the cellular localization of endothelin and its metabolizing enzyme, neutral endopeptidase, in endometrial biopsies from women with documented menorrhagia and in those with a normal menstrual cycle. Menorrhagia was documented by measurement of menstrual blood loss, 146 +/- 141 ml (median +/- SD). Endothelin and neutral endopeptidase were localized by immunohistochemistry, and the staining intensity was graded. Their immunostaining patterns were found to differ in menorrhagia compared to the normal menstrual cycle. Endothelin was reduced in glandular epithelium in menorrhagia and did not vary cyclically, while neutral endopeptidase was increased in the glandular epithelium. In menorrhagia, stromal endothelin immunoreactivity was not different from the normal cycle and although neutral endopeptidase immunostaining in stroma was similar to the secretory phase of normal endometrium, cyclical variation was absent. The potential for increased metabolism of endothelin could be an explanation for the decreased endothelin immunostaining in the glandular epithelium.   相似文献   
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