全文获取类型
收费全文 | 82篇 |
免费 | 12篇 |
国内免费 | 27篇 |
专业分类
121篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 5篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 2篇 |
2017年 | 6篇 |
2016年 | 3篇 |
2015年 | 3篇 |
2014年 | 3篇 |
2013年 | 6篇 |
2012年 | 8篇 |
2011年 | 12篇 |
2010年 | 7篇 |
2009年 | 3篇 |
2008年 | 7篇 |
2007年 | 4篇 |
2006年 | 9篇 |
2005年 | 3篇 |
2004年 | 5篇 |
2003年 | 3篇 |
2002年 | 1篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
排序方式: 共有121条查询结果,搜索用时 15 毫秒
81.
The presentation of microbial protein antigens by Major Histocompatibility Complex (MHC) molecules is essential for the development of acquired immunity to infections. However, most biochemical studies of antigen processing and presentation deal with a few relatively inert non-microbial model antigens. The bacterial pore-forming toxin listeriolysin O (LLO) is paradoxical in that it is cytotoxic at nanomolar concentrations as well as being the source of dominant CD4 and CD8 T cell epitopes following infection with Listeria monocytogenes. Here, we examined the relationship of LLO toxicity to its antigenicity and immunogenicity. LLO offered to antigen presenting cells (APC) as a soluble protein, was presented to CD4 T cells at picomolar to femtomolar concentrations- doses 3000-7000-fold lower than free peptide. This presentation required a dose of LLO below the cytotoxic level. Mutations of two key tryptophan residues reduced LLO toxicity by 10-100-fold but had no effect on its presentation to CD4 T cells. Thus there was a clear dissociation between the cytotoxic properties of LLO and its very high antigenicity. Presentation of LLO to CD8 T cells was not as robust as that seen in CD4 T cells, but still occurred in the nanomolar range. APC rapidly bound and internalized LLO, then disrupted endosomal compartments within 4 hours of treatment, allowing endosomal contents to access the cytosol. LLO was also immunogenic after in vivo administration into mice. Our results demonstrate the strength of LLO as an immunogen to both CD4 and CD8 T cells. 相似文献
82.
Saldanha JF Carrero JJ Lobo JC Stockler-Pinto MB Leal VO Calixto A Geloneze B Mafra D 《Regulatory peptides》2012,173(1-3):82-85
Nesfatin-1 is a recently identified anorexigenic peptide that has been implicated in appetite regulation, weight loss and/or malnutrition. Anorexia and malnutrition are common features of chronic kidney disease (CKD) that predispose patients to worse outcomes. However, the reasons for the occurrence of anorexia in CKD patients are not fully elucidated. The aim of this study was to investigate the association between nesfatin-1 and protein intake and body composition in patients undergoing hemodialysis (HD). Twenty five HD patients from a private Clinic in Rio de Janeiro, Brazil were studied and compared with 15 healthy subjects that were matched for body mass index (BMI), % body fat mass (by anthropometrics) and age. Appetite was measured using a specific questionnaire, and food intake was evaluated based on 3-day food records. Nesfatin-1 levels were measured by ELISA and leptin, TNF-α and IL-6 levels were determined by a multiplex assay kit. Serum nesfatin-1 levels did not differ between HD patients (0.16±0.07ng/mL) and healthy subjects (0.17±0.10ng/mL). Nesfatin-1 levels showed significant negative correlations with protein intake (r=-0.42; p=0.03), but did not associate with inflammatory markers or appetite scores. Combining patients and controls, we observed positive correlations with BMI (r=0.33; p=0.03), % body fat (r=0.35; p=0.03), leptin (r=0.45; p=0.006) and the triceps skinfold thickness (r=0.36; p=0.02). In multivariate analysis % body fat was the main determinant of nesfatin-1 variance. In conclusion, nesfatin-1 levels did not differ between HD patients and healthy subjects and negatively correlated with protein intake. This pathway is likely not dysregulated in uremia. 相似文献
83.
Fluorescence recovery after photobleaching (FRAP) is an experimental technique used to measure the mobility of proteins within
the cell nucleus. After proteins of interest are fluorescently tagged for their visualization and monitoring, a small region
of the nucleus is photobleached. The experimental FRAP data are obtained by recording the recovery of the fluorescence in
this region over time.
In this paper, we characterize the fluorescence recovery curves for diffusing nuclear proteins undergoing binding events with
an approximate spatially homogeneous structure. We analyze two mathematical models for interpreting the experimental FRAP
data, namely a reaction-diffusionmodel and a compartmental model. Perturbation analysis leads to a clear explanation of two
important limiting dynamical types of behavior exhibited by experimental recovery curves, namely, (1) a reduced diffusive
recovery, and (2) a biphasic recovery characterized by a fast phase and a slow phase. We show how the two models, describing
the same type of dynamics using different approaches, relate and share common ground. The results can be used to interpret
experimental FRAP data in terms of protein dynamics and to simplify the task of parameter estimation. Application of the results
is demonstrated for nuclear actin and type H1 histone. 相似文献
84.
Ciriza I Carrero P Azcoitia I Lundeen SG Garcia-Segura LM 《Journal of neurobiology》2004,61(2):209-221
Neuroprotective effects of estradiol are well characterized in animal experimental models. However, in humans, the outcome of estrogen treatment for cognitive function and neurological diseases is very controversial. Selective estrogen receptor modulators (SERMs) may represent an alternative to estrogen for the treatment or the prevention of neurodegenerative disorders. SERMs interact with the estrogen receptors and have tissue-specific effects distinct from those of estradiol, acting as estrogen agonists in some tissues and as antagonists in others. In this study we have assessed the effect of tamoxifen, raloxifene, lasofoxifene (CP-336,156), bazedoxifene (TSE-424), and 17beta-estradiol on the hippocampus of adult ovariectomized rats, after the administration of the excitotoxin kainic acid. Administration of kainic acid induced the expression of vimentin in reactive astroglia and a significant neuronal loss in the hilus. SERMs did not affect vimentin immunoreactivity in the hilus, while 17beta-estradiol significantly reduced the surface density of vimentin immunoreactive profiles. Estradiol, tamoxifen (0.4-2 mg/kg), raloxifene (0.4-2 mg/kg), and bazedoxifene (2 mg/kg) prevented neuronal loss in the hilus after the administration of kainic acid. Lasofoxifene (0.4-2 mg/kg) was not neuroprotective. These findings indicate that SERMs present different dose-dependent neuroprotective effects. Furthermore, the mechanisms of neuroprotection by SERMs and estradiol are not identical, because SERMs do not significantly affect reactive gliosis while neuroprotection by estradiol is associated with a strong down-regulation of reactive astroglia. 相似文献
85.
本文对云南首次分离到的Sindbis病毒进行了滤过试验,耐酸耐醚试验、致细胞病变、动物敏感性试验、血压 凝特性、空斑和毒力等试验研究,结果符合披膜病毒科的病毒特性。交 因抑试验和免疫荧光试验,以及空斑减小中和试验进一步证实为甲病毒属的Sindbis病毒,其空斑纯化株的生物学特性也与原株相符,纯化株的制备为该株病毒分子生物学研究的准确性和一致性提供了条件。云南Sindbis病毒的首次分离具有重要的流行病学意义,其生物学特性研究结果对我省该病的诊断和防治具有重要的指导意义。 相似文献
86.
L6565小鼠白血病病毒诱发小鼠白血病 总被引:4,自引:0,他引:4
为探讨病毒与白血病发生的关系,我们用L6565小鼠白血病病毒(L6565MLV)悬液感染乳鼠,每周观察小鼠的发病情况及病理变化,并用逆转录一聚合酶链反应(RT-PCR)动态检测小鼠体内病毒核酸的分布.结果发现小鼠感染病毒后3~5周,其脾脏和淋巴结呈早期白血病的病理改变.至第10~12周小鼠发生淋巴细胞白血病,表现出耸毛、活动减少、腹膨胀等症状.病毒核酸于感染后第2周首先在小鼠胸腺、脾脏检测到,随时间延长,病毒核酸广泛分布在外周血、胸腺、脾脏、淋巴结等多种脏器组织中.本实验表明L6565小鼠白血病病毒可诱发小鼠白血病,其机制可能与病毒促使淋巴细胞向白血病细胞转化有关. 相似文献
87.
目的:探讨血清甘油三酯(TG)与急性缺血性脑卒中(AIS)早期预测之间的相关性.方法:我们收集了736例AIS患者.依据TG水平将患者分为5组.参照美国国立卫生研究院(为什么不参照我国的标准)卒中量表(NIHSS),将早期神经功能恶化(END)设定为≥4分,将新发症状开始一周后的早期临床改善(ECI)定为降低4分或以上.将各组内的END、ECI患者及两者都不是的患者进行比较.结果:高TG和低TG组患者发生END的风险显著高于正常组.高TG、低TG组以及临界组患者发生ECI的百分率显著低于正常组.多元回归分析显示高TG、低TG组以及临界组患者在END中的or值显著高于正常低值组(50-100 mg/dl).AIS患者的甘油三酯(TG)水平与预后不良呈非线性的J型相关,与良好预后呈反J形相关.结论:在AIS的早期高TG和低TG都是预后不良的危险因素. 相似文献
88.
目的:构建增强型绿色荧光蛋白(EGFP)标记的乙型肝炎病毒(HBV)真核表达载体,并研究其在真核细胞和小鼠体内的共表达。方法:以质粒pBR322-HBVadr2.0和pCX-EGFP为基础,构建含有双拷贝HBV全基因组DNA和EGFP基因的真核表达载体pCX-EGFP-HBVadr2.0,分别转染真核细胞和小鼠肝组织,建立体外、体内表达系统,研究GFP和HBV基因的表达。结果:构建了真核表达载体pCX-EGFP-HBVadr2.0,EGFP和HBV病毒蛋白在体内和体外均可表达。结论:构建的pCX-EGFP-HBVadr2.0真核表达载体可以GFP作为HBV存在与否的报告基因,提高了培育检测转基因小鼠的效率,为转基因小鼠的制备及后续研究奠定了基础。 相似文献
89.
南京市2011年乙型流感血凝素基因分子特征分析 总被引:1,自引:0,他引:1
[目的]分析2011年南京市乙型流感病毒的血凝素(HA)分子学特征.[方法]选择7株2011年南京市不同时间段有代表性的乙型流感毒株进行HA基因序列测定,通过生物信息学方法对HA分子学特征进行分析.[结果]7株乙型流感毒株分为两个系,4株为Victoria,3株为Yamagata;与2011年度疫苗株相比,Victoria和Yamagata系毒株分别在抗原位点146、197和116、198发生了氨基酸替换;其中197和198位点分别是Victoria和Yamagata毒株的受体结合位点,由于上述位点的替换使得Victoria系/Yamagata系毒株分别在197/196位增加了一个潜在的糖基化位点.[结论]2011年南京市乙型流感Victoria 系和Yamagata系病毒同时存在,Victoria/Yamagata毒株197/198位点的氨基酸替换,值得做进一步的探讨. 相似文献
90.