全文获取类型
收费全文 | 63篇 |
免费 | 6篇 |
国内免费 | 1篇 |
专业分类
基础医学 | 3篇 |
临床医学 | 9篇 |
内科学 | 11篇 |
神经病学 | 1篇 |
特种医学 | 3篇 |
外科学 | 1篇 |
综合类 | 5篇 |
预防医学 | 1篇 |
药学 | 30篇 |
中国医学 | 1篇 |
肿瘤学 | 5篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 7篇 |
2014年 | 2篇 |
2013年 | 26篇 |
2012年 | 2篇 |
2011年 | 1篇 |
2010年 | 1篇 |
2009年 | 1篇 |
2008年 | 3篇 |
2007年 | 1篇 |
2006年 | 2篇 |
2004年 | 2篇 |
2003年 | 1篇 |
2000年 | 2篇 |
1995年 | 1篇 |
排序方式: 共有70条查询结果,搜索用时 15 毫秒
1.
The evolution of instrumentation in terms of separation and detection allowed a real improvement of the sensitivity and analysis time. However, the analysis of ultra-traces of toxins in complex samples requires often a step of purification and even preconcentration before their chromatographic analysis. Therefore, immunoaffinity sorbents based on specific antibodies thus providing a molecular recognition mechanism appear as powerful tools for the selective extraction of a target molecule and its structural analogs to obtain more reliable and sensitive quantitative analysis in environmental, food or biological matrices. This review focuses on immunosorbents that have proven their efficiency in selectively extracting various types of toxins of various sizes (from small mycotoxins to large proteins) and physicochemical properties. Immunosorbents are now commercially available, and their use has been validated for numerous applications. The wide variety of samples to be analyzed, as well as extraction conditions and their impact on extraction yields, is discussed. In addition, their potential for purification and thus suppression of matrix effects, responsible for quantification problems especially in mass spectrometry, is presented. Due to their similar properties, molecularly imprinted polymers and aptamer-based sorbents that appear to be an interesting alternative to antibodies are also briefly addressed by comparing their potential with that of immunosorbents. 相似文献
2.
乳腺癌是女性最常见的恶性肿瘤,实现乳腺癌的早期诊断和早期治疗意义重大.核酸适配体是经过指数富集配体系统进化技术(systematic evolution of ligands by exponential enrichment, SELEX)筛选得到的寡核苷酸序列,在肿瘤诊断及治疗方面拥有良好的应用前景.本文对靶向乳腺癌的核酸适配体及适配体作为载体和探针在乳腺癌诊疗中的作用进行综述. 相似文献
3.
《Expert opinion on therapeutic patents》2013,23(6):665-686
Introduction: The architecture of the complement system has evolved during the last 600 – 700 million years to become an amazingly efficient and highly versatile alerting and cell killing device. Under physiological conditions, this system acts as a well-regulated cascade, protecting the organism against pathogens and participating during the initial defensive steps of humoral and cellular response. The unregulated activation of this system may cause or even aggravate diseases; therefore, its modulation is currently considered of high importance. Areas covered: This review is a critical examination on patent literature published between 2008 and 2013. An insight is provided about the discovery and development of novel therapeutic agents. These include macromolecules, polysaccharides and proteins, specific antibodies, and hybrid or chimeric products. Peptides and low molecular weight organic compounds (natural products, their derivatives and fully synthetic molecules) are covered as well. Expert opinion: The search of specific inhibitors of the complement cascade has become one of the Holy Grails of Medicinal Chemistry for the last 30 – 40 years, with very few cases of success. Some highly specific macromolecules are currently available as modulators of the complement. However, there is still a marked need to find new, more specific, efficient and convenient alternatives, especially suited for chronic administration, including novel inexpensive small molecule inhibitors. Analogously, despite the initial success with specific monoclonal antibodies, a vast territory is awaiting to be explored and conquered, regarding the regulation of complement activation by antibody-mediated blockage of specific polypeptides or receptor sites. 相似文献
4.
Aptamers are short fragments of nucleic acids, DNA or RNA that have the ability to bind selected proteins with high specificity and affinity. These properties allow them to be used as an element of biosensors for the detection of specific proteins, including viral ones, which makes it possible to design valuable diagnostic tools. The influenza virus causes a huge number of human and animal deaths worldwide every year, and contributes to remarkable economic losses. In addition, in 2020, a new threat appeared—the SARS-Cov-2 pandemic. Both disease entities, especially in the initial stage of infection, are almost identical in terms of signs and symptoms. Therefore, a diagnostic solution is needed that will allow distinguishing between both pathogens, with high sensitivity and specificity; it should be cheap, quick and possible to use in the field, for example, in a doctor’s office. All the mentioned properties are met by aptasensors in which the detection elements are specific aptamers. We present here the latest developments in the construction of various types of aptasensors for the detection of influenza virus. Aptasensor operation is based on the measurement of changes in electric impedance, fluorescence or electric signal (impedimetric, fluorescence and electrochemical aptasensors, respectively); it allows both qualitative and quantitative determinations. The particularly high advancement for detecting of influenza virus concerns impedimetric aptasensors. 相似文献
5.
6.
《Expert opinion on therapeutic patents》2013,23(4):543-559
Oligonucleotide analogues containing nitrogen replacing either 3′- or 5′-oxygen atoms have been attracting attention of the scientific community for a long time. Originally, it was suggested that these compounds might be used as a functional mimetic of DNA molecules, which could be easier to prepare, due to a higher nucleophilicity of amino vis-a-vie hydroxyl group. Recent advances in development of oligonucleotide-based therapeutic and diagnostic agents significantly increased interest in these compounds as potential antisense and antigene compounds. Among numerous synthesised molecules the N3′→P5′ phosphoramidate oligonucleotides attract particular attention. Uniformly modified oligonucleotide N3′→P5′ phosphoramidates, containing 3′-amino replacing 3′-hydroxyl nucleosides, form very stable duplexes with complementary native phosphodiester DNA, and particularly with RNA strands. The phosphoramidate compounds form extremely stable triple-stranded complexes with single or double-stranded DNA targets and 2′-deoxyoligonucleotide N3′→P5′ phosphoramidates and their duplexes are structurally and functionally similar to those formed by native RNA molecules. This property allowed for application of these compounds as RNA decoys. Further duplex stabilisation was observed for 2′-deoxyoligonucleotide N3′→P5′ oligonucleotides. N3′→P5′ phosphoramidates oligonucleotides are highly resistant to enzymatic digestion by cellular nucleases and their duplexes with complementary RNA strands that are not substrates for RNase H-catalysed hydrolysis in vitro. However, they still exert sequence specific activity in various cellular systems and in vivo in mice, comparable or superior to RNase H-inducing phosphorothioate oligonucleotides. Fluorescently labelled phosphoramidates have also been used as FISH probes for telomeric DNA-directed diagnostic applications. 相似文献
7.
Michael Wood Xanthe Spindler Claude Roux Chris Lennard 《The Australian journal of forensic sciences》2013,45(2):211-226
Latent fingermark detection remains one of the most commonly utilised forensic practices when dealing with scenes of crime or related items. Although many options are available to detect and visualise these marks, the quest for techniques with greater sensitivity and selectivity continues. This has led to many improvements in detection methods and also numerous new techniques being developed. However, these have largely only led to incremental advancements despite the desire for transformational improvements. The use of immunology in the detection of latent fingermarks is an area that has been investigated more recently as a possible proposal to provide these transformational improvements, specifically to overcome sensitivity and selectivity issues currently seen with existing methods. This paper reviews the attempts to harness the detection capabilities of immunology and utilise them in the field of latent fingermark detection. Results achieved to date have highlighted many advantages and possibilities in detection and visualisation of latent marks, including the possibility of gaining ‘intelligence’ from the marks themselves. This paper also presents a brief introduction to the use of aptamers as the next logical step in immunogenic techniques for investigation. 相似文献
8.
《Expert opinion on drug discovery》2013,8(6):889-903
This is a review of RNA as a target for small molecules (ribosomes, riboswitches, regulatory RNAs) and RNA-derived oligonucleotides as tools (antisense/small interfering RNA, ribozymes, aptamers/decoy RNA and microRNA). This review highlights the present state of research using RNA as a drug target or as a potential drug candidate and explains at which stage and to what extent rational design could eventually be involved. Special attention has been paid to the recent potential clinical applications of RNA either as drugs or drug targets. The review deals mainly with mechanistic approaches rather than with physicochemical or computational aspects of RNA-based drug design. 相似文献
9.
Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are one of the important receptor classes involved in glutamate-mediated excitotoxicity. Although small molecule antagonists of this receptor have been shown to have neuroprotective properties, their low solubilities pose severe side effects in clinical trials. Here we have used the SELEX method to obtain water-soluble nuclease-resistant RNA ligands that bind to the agonist binding site of AMPA receptors. Using whole-cell current recordings, we have characterized the functional consequences of a representative aptamer from this class and show that it is a competitive antagonist of AMPA receptors and in the concentration range where it acts as an inhibitor of the AMPA receptor the RNA has no effect on the GluR6 homomeric kainate receptors. Additionally, using a fluorescence resonance energy transfer (FRET) probe, we show that this RNA ligand stabilizes the open cleft conformation of the ligand binding domain, consistent with the known structures of small antagonist-bound states of the soluble domain of this protein. Finally, using rat primary cortical neurons, we show that this RNA ligand significantly reduces neurotoxicity associated with oxygen glucose deprivation. The water-soluble and antagonistic properties of this aptamer coupled with its neuroprotective properties make it an excellent candidate for potential use in diseases or pathological conditions involving glutamate-mediated excitotoxicity. 相似文献
10.