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排序方式: 共有106条查询结果,搜索用时 15 毫秒
1.
N. Y. Calingasan S. E. Gandy H. Baker K. F. Sheu J. D. Smith B. T. Lamb J. D. Gearhart J. D. Buxbaum C. Harper D. J. Selkoe D. L. Price S. S. Sisodia G. E. Gibson 《The American journal of pathology》1996,149(3):1063-1071
Experimental thiamine deficiency (TD) is a classical model of a nutritional deficit associated with a generalized impairment of oxidative metabolism and selective cell loss in the brain. In rats, TD-induced cell degeneration is accompanied by an accumulation of amyloid precursor protein (APP)/amyloid precursor-like protein 2 (APLP2) immunoreactivity in abnormal neurites and perikarya along the periphery of, or scattered within, the lesion. Prompted by these data and our previous findings of a genetic variation in the development of TD symptoms, we extended our studies to mice. C57BL/6, ApoE knockout, and APP YAC transgenic mice received thiamine-deficient diet and pyrithiamine injections. Unlike rats, APP/APLP2-immunoreactive neurites in all strains of mice were sparsely scattered within damaged areas and did not delimit the thalamic lesion. In addition, abnormal clusters of intensely immunoreactive neurites occurred only in areas of damage including the thalamus, mammillary body, and inferior colliculus. The clusters appeared as either irregular clumps or round or oval rosettes that strikingly resembled the neuritic component of Alzheimer amyloid plaques. However, immunostaining using various antisera to synthetic amyloid beta-protein (A beta 1-40) and thioflavine S histochemistry failed to show evidence of a component of A beta Neither APP/APLP2-immunoreactive clusters nor amyloid plaques were observed in the brain from patients with Wernicke-Korsakoff syndrome, the clinical manifestation of TD in man. Our results demonstrate species (i.e., genetic) differences in the response to TD-induced damage and support a role for APP and APLP2 in the response to brain injury. This is the first report that chronic oxidative deficits can lead to this novel pathology. 相似文献
2.
Jiang WZ Jin NY Li ZJ Zhang LS Wang HW Zhang YJ Han WY 《第二军医大学学报》2006,27(4):434-434
To express the core protein of HIV-1 of Chinese prevalent strain (HIV-1 (CN)) in Pichia pastoris, the fulllength gag gene was inserted into the secretory expression vector pHILS1. Linearized recombinant plasmid pHILGAG by Sail was electrotransformed into the yeast strain GS115, and the yeast transformants were identified by PCR. To induce the interest protein to be expressed, the PCR positive transformants were inoculated in the medium of BMGY and BMMY, mRNA of the strain was detected by RT-PCR, and the expressed protein was analyzed by SDS-PAGE, Western blotting and thin layer scanning. mRNA (1.3 kb) was amplified by RT-PCR. SDS-PAGE and Western blotting analysis showed that the molecular mass of the expressed protein was 55 kD, which was similar to the expected value, and the expressed protein could react with McAb to HIV-1 p24. Thin layer scanning analysis demonstrated that the whole amount of the expressed protein was approximately 13 % of the soluble protein in the supernatant. The recombinant yeast had good genetic stability. The optimal expression conditions of the engineering yeast were as follows: BMMY medium, 80-90% of dissolved oxygen, 1% methanol, and 3-day-cultivation course. Gag proteins were expressed under the optimal expression condition and purified via gel filtration chromatography. The purity of the interest protein was up to 85 %. After the purified proteins were inoculated into BALB/c mice, the anti-HIV-1 antibodies in the immunized mice could be detected by Western blotting. 相似文献
3.
Lydie Boussicault Anne-Sophie Hérard Noel Calingasan Fanny Petit Carole Malgorn Nicolas Merienne Caroline Jan Marie-Claude Gaillard Rodrigo Lerchundi Luis F Barros Carole Escartin Thierry Delzescaux Jean Mariani Philippe Hantraye M Flint Beal Emmanuel Brouillet Céline Véga Gilles Bonvento 《Journal of cerebral blood flow and metabolism》2014,34(9):1500-1510
Huntington''s disease (HD) is caused by cytosine-adenine-guanine (CAG) repeat expansions in the huntingtin (Htt) gene. Although early energy metabolic alterations in HD are likely to contribute to later neurodegenerative processes, the cellular and molecular mechanisms responsible for these metabolic alterations are not well characterized. Using the BACHD mice that express the full-length mutant huntingtin (mHtt) protein with 97 glutamine repeats, we first demonstrated localized in vivo changes in brain glucose use reminiscent of what is observed in premanifest HD carriers. Using biochemical, molecular, and functional analyses on different primary cell culture models from BACHD mice, we observed that mHtt does not directly affect metabolic activity in a cell autonomous manner. However, coculture of neurons with astrocytes from wild-type or BACHD mice identified mutant astrocytes as a source of adverse non-cell autonomous effects on neuron energy metabolism possibly by increasing oxidative stress. These results suggest that astrocyte-to-neuron signaling is involved in early energy metabolic alterations in HD. 相似文献
4.
目的对自闭症病人给予被动性语言刺激,评价采用功能性磁共振(MR)成像作为判断病人有无语言缺陷的客观指标的可行性。材料与方法本研究为前瞻性研究,研究方 相似文献
5.
Neuroprotective mechanisms of creatine occur in the absence of mitochondrial creatine kinase 总被引:2,自引:0,他引:2
Klivenyi P Calingasan NY Starkov A Stavrovskaya IG Kristal BS Yang L Wieringa B Beal MF 《Neurobiology of disease》2004,15(3):610-617
There is substantial evidence that creatine administration exerts neuroprotective effects both in vitro and in vivo. The precise mechanisms for these neuroprotective effects however are as yet unclear. We investigated whether creatine administration could exert neuroprotective effects in mice deficient in ubiquitous mitochondrial creatine kinase (UbMi-CK). UbMi-CK-deficient mice showed increased sensitivity to 1-methyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced dopamine depletion and loss of tyrosine hydroxylase (TH) stained neurons. Isolated mitochondria from these mice showed no alterations in calcium retention, oxygen utilization, membrane potential, or swelling in response to a calcium challenge. Creatine administration significantly increased brain concentrations of both creatine and PCr in the UbMi-CK knockout mice. Creatine administration to the UbMi-CK-deficient mice exerted significant neuroprotective effects against MPTP toxicity that were comparable in magnitude to those seen in wild-type mice. These results suggest that the neuroprotective effects of creatine are not mediated by an effect on UbMi-CK to inhibit the mitochondrial permeability transition, and are more likely to be mediated by maintenance of appropriate ATP/ADP and PCr/Cr levels. 相似文献
6.
The influence of pretransplant lipoprotein abnormalities on the early results of renal transplantation 总被引:3,自引:0,他引:3
E. DIMÉNY G. TUFVESON† H. LITHELL‡ E. LARSSON§ A. SIEGBAHN¶ B. FELLSTRÖM 《European journal of clinical investigation》1993,23(9):572-579
Abstract. Lipoprotein patterns were investigated before and after renal transplantation in a prospective study including 151 patients. Kidney graft losses during the first 6 months were associated with higher total cholesterol ( P = 0.03), LDL cholesterol ( P = 0.003) and LDL triglyceride levels ( P = 0.01) before transplantation. Patients with serum cholesterol ±6.9 mmol l-1 before transplantation had more acute rejections (1.7 vs. 0.9), a worse graft function and more vascular intimal hyperplasia and glomerular mesangial changes in transplant biopsies at 6 months. Patients with serum creatinine levels exceeding 160 μmol l-1 at 6 months had more severe lipid disorders already before transplantation.
Serum creatinine at 6 months was influenced by the number of acute rejection episodes ( P = 0.0001) and the age of the donor ( P = 0.009) while the number of acute rejections was found to be related to pretrans plant total cholesterol levels ( P = 0.0086) and the age of the recipient ( P = 0.025).
In conclusion, pretransplant lipoprotein disturbances have an impact on the early outcome of renal transplantation. Since there is a progresssion of hyperlipidaemia following transplantation, this may have an influence also on the cardiovascular morbidity and late graft dysfunction. 相似文献
Serum creatinine at 6 months was influenced by the number of acute rejection episodes ( P = 0.0001) and the age of the donor ( P = 0.009) while the number of acute rejections was found to be related to pretrans plant total cholesterol levels ( P = 0.0086) and the age of the recipient ( P = 0.025).
In conclusion, pretransplant lipoprotein disturbances have an impact on the early outcome of renal transplantation. Since there is a progresssion of hyperlipidaemia following transplantation, this may have an influence also on the cardiovascular morbidity and late graft dysfunction. 相似文献
7.
目的:探讨心脏克隆钾离子通道Kv1.4的C型失活(Kv1.4△N)在非洲蟾蜍卵母细胞上表达后的动力学特性以及酸中毒时的改变。方法:将Kv1.4△N cRNA(最大体积为50 n1)注入非洲爪蟾的卵母细胞内,于18℃孵育16h以上。电极采用两步法拉制,微电极由1.5 mm口径的电极拉制。电极内充3M KCl,电阻0.5~1.0MΩ。采用双微电极电压钳制法(two electrode voltage clamp,TEV)在室温下(20~24℃)记录电流。结果:与正常pH时相比,酸性环境下,Kv1.4△N的峰电流减小,在pH7.4时通道在去极化至-40mv激活,而pH 6.8时为-30mv激活;通道在pH 7.4时最大失活为0.384±0.072,而在pH6.8时为0.197±0.013;在pH6.8时通道复活减慢(P<0.05)。结论:酸中毒导致通道电流减小,并且使通道失活加快和恢复减慢。 相似文献
8.
Michel Kahaleh Everson LA Artifon Manuel Perez-Miranda Kapil Gupta Takao Itoi Kenneth F Binmoeller California Pacific Medical Center San Francisco CA United States Marc Giovannini 《World journal of gastroenterology : WJG》2013,19(9):1372-1379
Endoscopic retrograde cholangiopancreatography (ERCP) has become the preferred procedure for biliary or pancreatic drainage in various pancreatico-biliary disorders. With a success rate of more than 90%, ERCP may not achieve biliary or pancreatic drainage in cases with altered anatomy or with tumors obstructing access to the duodenum. In the past those failures were typically managed exclusively by percutaneous approaches by interventional radiologists or surgical intervention. The morbidity associated was significant especially in those patients with advanced malignancy, seeking minimally invasive interventions and improved quality of life. With the advent of biliary drainage via endoscopic ultrasound (EUS) guidance, EUS guided biliary drainage has been used more frequently within the last decade in different countries. As with any novel advanced endoscopic procedure that encompasses various approaches, advanced endoscopists all over the world have innovated and adopted diverse EUS guided biliary and pancreatic drainage techniques. This diversity has resulted in variations and improvements in EUS Guided biliary and pancreatic drainage; and over the years has led to an extensive nomenclature. The diversity of techniques, nomenclature and recent progress in our intrumentation has led to a dedicated meeting on May 7 th , 2011 during Digestive Disease Week 2011. More than 40 advanced endoscopists from United States, Brazil, Mexico, Venezuela, Colombia, Italy, France, Austria, Germany, Spain, Japan, China, South Korea and India attended this pivotal meeting. The meeting covered improved EUS guided biliary access and drainage procedures, terminology, nomenclature, training and credentialing; as well as emerging devices for EUS guided biliary drainage. This paper summarizes the meeting’s agenda and the conclusions generated by the creation of this consortium group. 相似文献
9.
P. ARENBERGER L. KEMÉNY † T. RUZICKA ‡ 《European journal of clinical investigation》1992,22(4):235-243
12-hydroxyeicosatetraenoic acid (12-HETE) is assumed to play a central role in the pathophysiology of psoriasis. Since its effects in skin are mediated by specific high-affinity receptors, we studied the receptor characteristics in cultured epidermal cells from involved and apparently healthy skin of psoriasis patients by radioligand binding assay. Involved and uninvolved psoriatic epidermal cells showed a fourfold decrease in the number of 12-HETE binding sites as compared with normal healthy individuals and patients with atopic dermatitis, while receptor affinity remained unchanged. The decrease in receptor number was evident in psoriatic cells even in long-term culture and was not due to receptor down-regulation, defective response to interferon gamma or to protease degradation of receptor protein. The decrease in the number of 12-HETE receptors detectable even in clinically normal psoriatic skin functionally leads to diminished 12-HETE uptake and may thus represent a primary central molecular defect in the pathophysiology of the disease. 相似文献
10.
Petri S Kiaei M Wille E Calingasan NY Flint Beal M 《Journal of the neurological sciences》2006,251(1-2):44-49
ALS is a devastating neurodegenerative disorder for which no effective treatment exists. The precise molecular mechanisms underlying the selective degeneration of motor neurons are still unknown. A motor neuron specific apoptotic pathway involving Fas and NO has been discovered. Motor neurons from ALS-mice have an increased sensitivity to Fas-induced cell death via this pathway. In this study we therefore crossed G93A-SOD1 overexpressing ALS mice with Fas ligand (FasL) mutant (gld) mice to investigate whether the reduced Fas signaling could have beneficial effects on motor neuron death. G93A-SOD1 mutant mice with a homozygous FasL mutant showed a modest but statistically significant extension of survival, and reduced loss of motor neurons. These results indicate that motor neuron apoptosis triggered by Fas is relevant in ALS pathogenesis. 相似文献