锌离子与Aβ多肽中氨基酸结合能力次序的研究

阐明金属离子的稳态失衡是导致老年痴呆病人脑部Aβ多肽发生聚集的因素之一,金属离子与Aβ多肽的结合位点是开发靶向药物的关键所在.采用紫外分光光度法,首次对生理条件下锌离子与Aβ多肽中氨基酸的络合作用进行了研究,得到了该条件下络合物的稳定常数大小,指出了锌离子-Aβ多肽可能的结合位点,这一结果对深入了解金属离子在诱导老年痴呆过程中的协同作用以及金属鳌合剂药物治疗提供实验支持.     

蛋白质和多肽药物质量控制中分析方法的应用概况

蛋白质和多肽药物研究进展迅速,蛋白质和多肽药物的分析方法和相关检测设备也在不断地更新和改进,从而为该类药物的开发研究、质量控制和临床应用都提供了重要的手段。     

蛋白质的PEG化学修饰

目的蛋白、多肽等药物分子免疫原性和毒副反应的存在及体内作用时间短等问题限制了其应用,这可以通过化学修饰部分或全部加以克服。随着蛋白质构效关系的揭示,蛋白质的化学修饰的研究飞速发展。此文对蛋白质、多肽等药物分子化学修饰的国内外研究进展和发展方向加以评述。     

天然多肽分离方法及其应用前景

综述了近几年来多肽物质主要分离方法,主要包括高效液相色谱法、电泳等方法,并概述了多肽在多肽药物、多肽食品、及多肽护肤品方面的应用。     

多肽序列优化降低c-Src蛋白靶向药物的毒性风险

避免c-Src蛋白的多肽类拮抗剂与多个蛋白发生混杂性结合,对于降低抗癌药物的毒性风险具有重要作用。本研究运用生物信息学方法对氨基酸序列进行优化设计,旨在减少混杂性结合的发生。本研究综合利用各种多肽数据库和生物信息学工具,首先总结了多肽分子与多个蛋白SH3结构域之间潜在的混杂性结合,并发现了其中的内在规律。随后,根据所发现的规律,对多肽的氨基酸序列进行针对性的优化设计。结果表明,大多数多肽在经过优化后,所结合的c-Src以外的蛋白数量都有所下降,从而显著提高了多肽与c-Src蛋白之间结合的特异性(P0.05),并降低了其潜在的毒性风险。本研究所取得的结果将为设计具有高度特异性和低毒性的靶向性多肽药物提供参考。     

抗菌多肽的研究进展

抗菌多肽是在生物体中具有抗菌活性的肽类物质的总称，是无数动植物天然免疫系统的重要组成部分，具有抗菌谱广、作用强且迅速、不易产生耐药等优点。抗菌多肽已经成为药物开发的研究热点。本文简要介绍抗菌多肽的分类、作用和作用机理，并对抗菌多肽的应用前景及其存在问题进行分析。     

抗菌多肽的研究进展

抗菌多肽是在生物体中具有抗菌活性的肽类物质的总称,是无数动植物天然免疫系统的重要组成部分,具有抗菌谱广、作用强且迅速、不易产生耐药等优点。抗菌多肽已经成为药物开发的研究热点。本文简要介绍抗菌多肽的分类、作用和作用机理,并对抗菌多肽的应用前景及其存在问题进行分析。     

靶向细胞凋亡的海洋抗肿瘤多肽药物研究进展

凋亡在肿瘤的形成和发展中具有重要功能,靶向凋亡通路已成为发展化疗药物的重要策略。海洋生物多肽是抗肿瘤药物的重要来源,并且已经发现的大多数抗肿瘤海洋多肽都可以通过诱导凋亡途径发挥抗肿瘤作用。本文针对这类海洋药物研发中存在的药物抗原性及药物来源等主要问题,综述了近年来发现的海洋多肽及其诱导细胞凋亡的信号通路。     

胃癌细胞SGC-7901双向电泳系统的建立及优化

文蛤抗癌活性多肽对多种癌细胞有抑制效应,具有良好的药物开发前景.双向电泳技术的进步为药物的开发提供了理想的技术平台.我们通过对胃癌细胞SGC-7901总蛋白双向电泳技术的建立以及初步优化对一些环节如样品处理的方法、上样量的选择、电泳参数的设置、凝胶浓度和SDS凝胶电泳染色方法等进行了优化得到了分辨率较好的胃癌细胞的蛋白图谱,为进一步的文蛤抗癌多肽抑制胃癌细胞作用的蛋白组学研究提供实验工作的基础.     

细胞穿膜肽在药物传递系统中的应用

细胞穿膜肽是一类能够穿透细胞膜并且不损坏细胞膜结构的小分子多肽,该多肽由不多于40个氨基酸组成。研究表明,将细胞穿膜肽与小分子药物、蛋白质以及纳米载体(如脂质体等)结合起来,促进这类药物或载体穿透肿瘤细胞膜,从而实现对肿瘤细胞的靶向性。该文重点介绍细胞穿膜肽的特点,作用机制以及它在药物传递系统中的应用。     

Markedness and its Interpretation in Language Use

Language markedness is a common phenomenon in languages, and is reflected from hearing, vision and sense, i.e. the variation in the three aspects such as phonology, morphology and semantics. This paper focuses on the interpretation of markedness in language use following the three perspectives, i.e. pragmatic interpretation, psychological interpretation and cognitive interpretation, with an aim to define the function of markedness.     

Features of Women's language

Language is a means of verbal communication. People use language to communicate with each other. In the society, no two speakers are exactly alike in the way of speaking. Some differences are due to age, gender, statue and personality. Above all, gender is one of the obvious reasons. The writer of this paper tries to describe the features of women＇s language from these perspectives： pronunciation, intonation, diction, subjects, grammar and discourse. From the discussion of the features of women＇s language, more attention should be paid to language use in social context. What＇s more, the linguistic phenomena in a speaking community can be understood more thoroughly.     

An Analysis of Catherine＇s Character——Wuthering Heights

Wuthering Heights, Emily Bronte＇s only novel, was published in December of 1847 under the pseudonym Ellis Bell. The book did not gain immediate success, but it is now thought one of the finest novels in the English language. Catherine is the key character of this masterpiece, because everybody and everything center on her though she had a short life. We can understand this masterpiece better if we know Catherine well.     

Lower Paleozoic oil relationships within Williston Basin, Canada

The Williston Basin is a significant petroleum province, containing oil production zones that include the Middle Cambrian to Lower Ordovician, Upper Ordovician, Middle Devonian, Upper Devonian and Mississippian and within the Jurassic and Cretaceous. The oils of the Williston Basin exhibit a wide range of geochemical characteristics defined as "oil families", although the geochemical signature of the Cambrian Deadwood Formation and Lower Ordovician Winnipeg reservoired oils does not match any "oil family". Despite their close stratigraphic proximity, it is evident that the oils of the Lower Palaeozoic within the Williston Basin are distinct. This suggests the presence of a new "oil family" within the Williston Basin. Diagnostic geochemical signatures occur in the gasoline range chromatograms, within saturate fraction gas chromatograms and biomarker fingerprints. However, some of the established criteria and cross-plots that are currently used to segregate oils into distinct genetic families within the basin do not always meet with success, particularly when applied to the Lower Palaeozoic oils of the Deadwood and Winnipeg Formation.     

低渗透非均质砂岩油藏启动压力梯度研究

理论推导与室内实验相结合,建立了低渗透非均质砂岩油藏启动压力梯度确定方法。首先借助油藏流场与电场相似的原理,推导了非均质砂岩油藏启动压力梯度计算公式。其次基于稳定流实验方法,建立了非均质砂岩油藏启动压力梯度测试方法。结果表明:低渗透非均质砂岩油藏的启动压力梯度确定遵循两个等效原则。平面非均质油藏的启动压力梯度等于各级渗透率段的启动压力梯度关于长度的加权平均;纵向非均质油藏的启动压力梯度等于各渗透率层的启动压力梯度关于渗透率与渗流面积乘积的加权平均。研究成果可用于有效指导低渗透非均质砂岩油藏的合理井距确定,促进该类油藏的高效开发。     

On Tragic Consciousness In The Works By Ernest Hemingway

As an American modern novelist who were famous in the literary world, Hemingway was not a person who always followed the trend but a sharp observer. At the same time, he was a tragedy maestro, he paid great attention on existence, fate and end-result. The dramatis personae's tragedy of his works was an extreme limit by all means tragedy on the meaning of fearless challenge that failed. The beauty of tragedy was not produced on the destruction of life, but now this kind of value was in the impact activity. They performed for the reader about the tragedy on challenging for the limit and the death.     

Design and analysis of generic LBS application developing platform

Location based services is promising due to its novel working style and contents.A software platform is proposed to provide application programs of typical location based services and support new applications developing efficiently. The analysis shows that this scheme is easy implemented, low cost and adapt to all kinds of mobile nework system.     

Achieving Unusual States of Matter Under High Pressure

正The periodicity of the elements and the non-reactivity of the inner-shell electrons are two related principles of chemistry,rooted in the atomic shell structure.Within compounds,Group I elements,for example,invariably assume the+1 oxidation state,and their chemical properties differ completely from those of the p-block elements.These general rules govern our understanding of chemical structures and reactions.Using first principles calcula-     

Exchange-Correlation and Electronic Excitation Energies from Pairing Matrix Fluctuations

We have developed an adiabatic connection to formulate the ground-state exchange-correlation energy in terms of pairing matrix linear fluctuations.This formulation of the exchange-correlation energy opens a new channel for density functional approximations based on the many-body perturbation theory.We illustrate the potential of such approaches with an approximation based on the particle-particle Random Phase Approximation(pp-RPA).This re-     

Density Functional Theory for the Response of Periodic Systems to Electric Fields Based on the Vector Potential Approach

正The electronic and nuclear(structural/vibrational)response of 1D-3D nanoscale systems to electric fields gives rise to a host of optical,mechanical,spectral,etc.properties that are of high theoretical and applied interest.Due to the computational difficulty of treating such large systems it is convenient to model them as infinite and periodic(at least,in first approximation).The fundamental theoretical/computational problem in doing so is that