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11.
Zantour B Guilhaume B Tissier F Louvel A Jeunemaitre X Gimenez-Roqueplo AP Bertagna X 《European journal of endocrinology / European Federation of Endocrine Societies》2004,151(4):433-438
A 32-year-old asymptomatic female was diagnosed with an isolated thyroid nodule of 2.5 cm diameter. Fine needle aspiration suggested a medullary thyroid carcinoma. Consequently, a total thyroidectomy was performed. The nodule stained positive for chromogranin A, neurone-specific enolase and synaptophysin, but not for calcitonin. Finally, pathological analysis showed a thyroid paraganglioma. Although the tumour appeared to be sporadic in a patient with no personal or familial history of paraganglioma and/or pheochromocytoma, we have identified a new mutation (392delC) of the succinate dehydrogenase-B (SDHB) gene in the genomic DNA extracted from the leukocytes of the patient. That mutation induced a shift in the reading frame of the gene creating a premature stop codon (P131fsX135) which was predicted to result in a truncated SDHB protein of 135 amino acids.This report highlights the difficulties of this unexpected diagnosis of hereditary thyroid paraganglioma. It also discusses the clinical involvements in terms of familial screening and the necessary follow-up of the patient. 相似文献
12.
Ehninger G; Schuler U; Renner U; Ehrsam M; Zeller KP; Blanz J; Storb R; Deeg HJ 《Blood》1995,85(11):3247-3249
In a canine model we investigated the toxicity and pharmacokinetics of a water soluble busulfan preparation. Busulfan was dissolved in dimethylsulfoxide (DMSO) and administered either orally or intravenously in a single dose of 1 mg/kg. The application in either preparation was well tolerated. In seven dogs, peak levels in the range of 730 ng/mL to 1,000 ng/mL were measured after intravenous injection with an area under curve (AUC) of 75 ng.h/kg.mL to 146 ng.h/kg.mL. It was of note that even the oral administration of the same busulfan preparation resulted in AUC values in the same range as observed after parenteral application. The absorption rate of busulfan tablets in our model was as unpredictable as documented in clinical trials. On the basis of the present study, clinical trials using busulfan dissolved in DMSO given either intravenously or orally appear warranted. This approach should lead to predictable blood levels, reduced toxicity, and increased efficacy of busulfan-containing regimens. 相似文献
13.
Goan SR; Fichtner I; Just U; Karawajew L; Schultze W; Krause KP; von Harsdorf S; von Schilling C; Herrmann F 《Blood》1995,86(1):89-100
Mononuclear cells (MNCs) containing peripheral blood stem cells (PBSCs) were obtained from solid-tumor patients undergoing mobilizing chemotherapy followed by granulocyte colony-stimulating factor for PBSC transplantation-supported dose-intensified anticancer chemotherapy and were transplanted into unconditioned "nonleaky" young severe combined immunodeficient mice. Multilineage engraftment was shown by flow cytometry and immunocytochemistry using monoclonal antibodies to various human cell surface antigens as well as identification of human immunoglobulin in murine sera. Within a dose range of MNCs suitable for transplantation (10 to 36 x 10(6) cells/graft) the number of CD34+ cells injected (optimal at > 0.7 x 10(6)/graft) determined the yield of human cells produced in recipient animals. Engraftment of hu PBSC preparations resulted in prolonged generation of physiologic levels of human cytokines including interleukin-3 (IL-3), IL-6, and granulocyte- macrophage colony-stimulating factor, which were detectable in the murine blood over a period of at least 4 months. In vivo survival of immature human progenitor cells was preserved even 9 months after transplantation. Because human IL-3 is known to stimulate early hematopoiesis, a rat fibroblast cell line was stably transfected with a retroviral vector carrying the human IL-3 gene and cotransplanted subcutaneously as additional source of growth factor. Cotransplants of this cell line producing sustained in vivo levels of circulating human IL-3 for at least 12 weeks significantly accelerated the process of engraftment of huPBSC and spurred the spread of mature human cells to the murine spleen, liver, thymus, and peripheral blood. Cotransplants of allogeneic human bone marrow stromal cells derived from long-term cultures resulted in a comparable--though less prominent--support of engraftment. 相似文献
14.
Plouin PF Gimenez-Roqueplo AP La Batide Alanore A Salenave S Duclos JM 《La Revue de médecine interne / fondée ... par la Société nationale francaise de médecine interne》2000,21(12):1075-1085
INTRODUCTION: Pheochromocytoma is a catecholamine-secreting neoplasm of chromaffin tissue. It is a rare disease. Biochemical tests should be performed only in patients at high risk of pheochromocytoma, and an imaging procedure only in those with positive biochemical tests. CURRENT KNOWLEDGE AND KEY POINTS: The most specific and sensitive diagnostic test for the disease is the determination of plasma or urinary metanephrines. The tumor can be located by computerized tomography, magnetic resonance imaging, and specific scintigraphy. Ten to 20% of pheochromocytomas result from hereditary diseases, including multiple endocrine neoplasia type 2, von Hippel Lindau disease, and neurofibromatosis 1. Familial cases are diagnosed earlier, and are more frequently bilateral and recurring than sporadic cases. About 10% of the cases are malignant either at first operation or during follow-up, malignancy being diagnosed by the presence of lymph node, visceral or bone metastases. The probability of a recurrence is positively correlated with the urinary excretion of metanephrines and tumor size. Recurrences are more frequent in cases with ectopic tumors and in those with a low plasma epinephrine to total catecholamine ratio. Patients, especially those with familial tumors or low epinephrine secretion, should be followed-up indefinitely. FUTURE PROSPECTS AND PROJECTS: Treatment for malignant recurrences includes surgery, therapeutic embolization, chemotherapy, and the application of therapeutic doses of metaiodobenzylguanidine. Metyrosine, phenoxybenzamine, or somatostatin analogs may help to control blood pressure and to alleviate symptoms in patients with malignant pheochromocytoma; however such a treatment has no antiproliferative effect. 相似文献
15.
Comparison of the subacute toxicity and efficacy of 3-hydroxypyridin-4- one iron chelators in overloaded and nonoverloaded mice 总被引:3,自引:1,他引:3
Five orally effective iron chelators of the 3-hydroxypyridin-4-one series have been administered intraperitoneally to iron-overloaded and nonoverloaded male mice at a dose of 200 mg/kg/24 h for a total of 60 days to investigate the effect on iron loading and toxicity. There was a significant reduction in hepatic iron at the end of the study in the iron-overloaded mice with all compounds studied using chemical iron quantitation (P less than .001) and with Perls' stain (P less than .01). Liver iron removal with the hydroxypyridinones ranged from 37% with CP20 to 63% with CP51, compared with 46% removal for desferrioxamine (DFO). There was no significant reduction in splenic or cardiac iron with any chelator. There were no deaths in iron-overloaded animals receiving any of the hydroxypyridin-4-ones, but significantly more deaths in the nonoverloaded groups as a whole (P less than .03). No weight loss was observed with any chelator. Significant reductions in hemoglobin and white cell count were observed with CP20(L1). No histologic abnormalities of kidney, spleen, bone marrow, or stifle joints were observed. Intracytoplasmic inclusion bodies were observed in the centrilobular hepatocytes of animals administered each of the hydroxypyridin-4-ones, while the DFO-treated and control groups showed no such changes. 相似文献
16.
Shilpa S Shetty Kumari N Suchetha Devi Harshini KP Sharmila Srinidhi Rai 《African health sciences》2020,20(4):1770
BackgroundMany risk factors contribute to the pathogenesis of diabetes. Gene and lifestyle factors are considered to be the major contributors. A dietary pattern is attributed to be one of the lifestyle risk factors favoring diabetes. The present study aims to find an association between fatty acid desaturase (FADS) gene polymorphism and glycemic profile in type 2 diabetes mellitus (T2DM).MethodologyA total of 429 subjects were included in the study on the basis of inclusion and exclusion criteria, of which 213 and 216 subjects were diabetic and control, respectively. Body mass index was calculated. Fasting plasma glucose, glycated hemoglobin (HbA1c) and insulin were measured using commercially available kits. rs174575 of FADS2 was selected based on previous publications and identified using the dbSNP database. To compare the biochemical parameters with the genotype, the following three models were used: additive model (CC vs CG vs GG), dominant model (CC + CG vs GG), and recessive model (CC vs CG + GG).Results and DiscussionFBS, HbA1c, insulin, HOMA-IR, and HOMA-B exhibited a high and statistically significant difference between subjects and controls. The three models exhibited a statistically significant difference between FBS, HOMA-IR, and HOMA- B (p<0.05).ConclusionThe distribution of rs174575 genotype differed significantly between the subjects and controls in the present study. The study revealed that genetic variation in FADS2 is an additional facet to consider while studying the risk factors of T2DM. 相似文献
17.
Hui Jun Lim Adrian Kah Heng Chiow Lip Seng Lee Siong San Tan Brian KP Goh Ye Xin Koh Chung Yip Chan Ser Yee Lee 《Singapore medical journal》2021,62(4):182
INTRODUCTIONFluorescence imaging (FI) with indocyanine green (ICG) is increasingly implemented as an intraoperative navigation tool in hepatobiliary surgery to identify hepatic tumours. This is useful in minimally invasive hepatectomy, where gross inspection and palpation are limited. This study aimed to evaluate the feasibility, safety and optimal timing of using ICG for tumour localisation in patients undergoing hepatic resection.METHODSFrom 2015 to 2018, a prospective multicentre study was conducted to evaluate feasibility and safety of ICG in tumour localisation following preoperative administration of ICG either on Day 0–3 or Day 4–7.RESULTSAmong 32 patients, a total of 46 lesions were resected: 23 were hepatocellular carcinomas (HCCs), 12 were colorectal liver metastases (CRLM) and 11 were benign lesions. ICG FI identified 38 (82.6%) lesions prior to resection. The majority of HCCs were homogeneous fluorescing lesions (56.6%), while CLRM were homogeneous (41.7%) or rim-enhancing (33.3%). The majority (75.0%) of the lesions not detected by ICG FI were in cirrhotic livers. Most (84.1%) of ICG-positive lesions detected were < 1 cm deep, and half of the lesions ≥ 1 cm in depth were not detected. In cirrhotic patients with malignant lesions, those given ICG on preoperative Day 0−3 and Day 4−7 had detection rates of 66.7% and 91.7%, respectively. There were no adverse events.CONCLUSIONICG FI is a safe and feasible method to assist tumour localisation in liver surgery. Different tumours appear to display characteristic fluorescent patterns. There may be no disadvantage of administering ICG closer to the operative date if it is more convenient, except in patients with liver cirrhosis. 相似文献
18.
KP Morris JR Skinner C Wren S Hunter MG Coulthard 《Archives of disease in childhood》1993,68(5):637-643
Thirteen anaemic children on dialysis were assessed to determine the incidence of cardiac changes in end stage renal failure. Nine children had an increased cardiothoracic ratio on radiography. The electrocardiogram was abnormal in every case but no child had left ventricular hypertrophy as assessed by voltage criteria. However, left ventricular hypertrophy, often gross, was found on echocardiography in 12 children and affected the interventricular septum disproportionately. Cardiac index was increased in 10 patients as a result of an increased left ventricular stroke volume rather than heart rate. Left ventricular hypertrophy was significantly greater in those on treatment for hypertension and in those with the highest cardiac index. Abnormal diastolic ventricular function was found in 6/11 children. Children with end stage renal failure have significant cardiac abnormalities that are likely to contribute to the high cardiovascular mortality in this group. Anaemia and hypertension, or its treatment, probably contribute to these changes. Voltage criteria on electrocardiogram are of no value in detecting left ventricular hypertrophy. Echocardiography must be performed, with the results corrected for age and surface area, in order to detect and follow these abnormalities. 相似文献
19.
Mitochondrial succinate is instrumental for HIF1alpha nuclear translocation in SDHA-mutant fibroblasts under normoxic conditions 总被引:2,自引:0,他引:2
Brière JJ Favier J Bénit P El Ghouzzi V Lorenzato A Rabier D Di Renzo MF Gimenez-Roqueplo AP Rustin P 《Human molecular genetics》2005,14(21):3263-3269
The genes encoding succinate dehydrogenase (SDH) subunits B, C and D, act as tumour suppressors in neuro-endocrine tissues. Tumour formation has been associated with succinate accumulation. In paraganglioma cells, two forms of SDHA (type I, II) were found which might preclude significant succinate accumulation in the case of a mutation in either form. In fibroblasts only SDHA type I is found. In these cells, SDHA type I mutation leads to SDH deficiency, succinate accumulation and hypoxia-inducible factor 1alpha(HIF1alpha) nuclear translocation. HIF1alpha nuclear translocation was not observed in ATPase-deficient fibroblasts with increased superoxide production and was found to be independent of cellular iron availability in SDHA-mutant cells. This suggests that neither superoxides nor iron were causative of HIF1alpha nuclear translocation. Conversely, alpha-ketoglutarate (alpha-KG) inhibits this nuclear translocation. Therefore, the pseudo-hypoxia pathway in SDH-deficient cells depends on the HIF1alphaprolyl hydroxylase product/substrate (succinate/alpha-KG) equilibrium. In SDH deficiency, organic acids thus appear instrumental in the HIF1alpha-dependent cascade suggesting a direct link between SDH and tumourigenesis. 相似文献
20.