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61.
62.
Advancing Small‐Molecule‐Based Chemical Biology with Next‐Generation Sequencing Technologies
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Chandran Anandhakumar Seiichiro Kizaki Dr. Toshikazu Bando Dr. Ganesh N. Pandian Prof. Dr. Hiroshi Sugiyama 《Chembiochem : a European journal of chemical biology》2015,16(1):20-38
Next‐generation‐sequencing (NGS) technologies enable us to obtain extensive information by deciphering millions of individual DNA sequencing reactions simultaneously. The new DNA‐sequencing strategies exceed their precursors in output by many orders of magnitude, resulting in a quantitative increase in valuable sequence information that could be harnessed for qualitative analysis. Sequencing on this scale has facilitated significant advances in diverse disciplines, ranging from the discovery, design, and evaluation of many small molecules and relevant biological mechanisms to maturation of personalized therapies. NGS technologies that have recently become affordable allow us to gain in‐depth insight into small‐molecule‐triggered biological phenomena and empower researchers to develop advanced versions of small molecules. In this review we focus on the overlooked implications of NGS technologies in chemical biology, with a special emphasis on small‐molecule development and screening. 相似文献
63.
核酸适配体是通过指数富集配体系统进化技术经体外筛选得到的可以特异性地识别目标物的一段短的单链寡核苷酸序列。与抗体相比,适配体具有性质稳定、易化学合成、易化学修饰、分子量小和目标分子广泛等优点,目前在生物传感器、毛细管电泳、物质分离富集以及医疗诊断等领域得到了广泛应用。本文重点介绍了核酸适配体在固相萃取、磁分离、亲和色谱及微流控分离分析等样品前处理技术中的应用,并对其应用现状和发展前景进行了综述。 相似文献
64.
Tatjana Schamber Oliver Binas Dr. Andreas Schlundt Anna Wacker Prof. Dr. Harald Schwalbe 《Chembiochem : a European journal of chemical biology》2022,23(3):e202100564
Riboswitches are regulatory RNA elements that undergo functionally important allosteric conformational switching upon binding of specific ligands. The here investigated guanidine-II riboswitch binds the small cation, guanidinium, and forms a kissing loop-loop interaction between its P1 and P2 hairpins. We investigated the structural changes to support previous studies regarding the binding mechanism. Using NMR spectroscopy, we confirmed the structure as observed in crystal structures and we characterized the kissing loop interaction upon addition of Mg2+ and ligand for the riboswitch aptamer from Escherichia coli. We further investigated closely related mutant constructs providing further insight into functional differences between the two (different) hairpins P1 and P2. Formation of intermolecular interactions were probed by small-angle X-ray scattering (SAXS) and NMR DOSY data. All data are consistent and show the formation of oligomeric states of the riboswitch induced by Mg2+ and ligand binding. 相似文献
65.
Dr. Nathalie Busschaert Dr. Debabrata Maity Dr. Pralok K. Samanta Prof. Niall J. English Prof. Andrew D. Hamilton 《Chembiochem : a European journal of chemical biology》2022,23(6):e202100670
The thrombin binding aptamer (TBA) is a 15-mer DNA oligonucleotide (5′-GGT TGG TGT GGT TGG-3′), that can form a stable intramolecular antiparallel chair-like G-quadruplex structure. This aptamer shows anticoagulant properties by interacting with one of the two anion binding sites of thrombin, namely the fibrinogen-recognition exosite. Here, we demonstrate that terminal modification of TBA with aromatic fragments such as coumarin, pyrene and perylene diimide (PDI), improves the G-quadruplex stability. The large aromatic surface of these dyes can π-π stack to the G-quadruplex or to each other, thereby stabilizing the aptamer. With respect to the original TBA, monoPDI-functionalized TBA exhibited the most remarkable improvement in melting temperature (ΔTm≈+18 °C) and displayed enhanced anticoagulant activity. 相似文献
66.
Xi‐Le Hu Nahyun Kwon Kai‐Cheng Yan Adam C. Sedgwick Guo‐Rong Chen Xiao‐Peng He Tony D. James Juyoung Yoon 《Advanced functional materials》2020,30(13)
Human beings are “machines” that use endogenously produced biomolecules as “components” in signaling and for the maintenance of the body. These biomolecules consist of proteins, nucleic acids, and carbohydrates, which can either be extracted from biological substrates or synthesized by chemical/biochemical methods. These biomolecules have the ability to recognize/interact with other biomolecules that are overexpressed in disease cells. For targeted theranostics, strategies to chemically incorporate these natural biomolecules with advanced materials to treat human diseases by imaging‐guided drug delivery or photodynamic/photothermal therapy are proposed, with improved biocompatibility. Herein, recent research on construction of quantum dots, nanoparticles, and 2D material platforms decorated with antibodies, peptides, nucleic acid aptamers, carbohydrates, and folic acid for targeted diagnosis and treatment are summarized and discussed. In addition, the various strategies required to construct effective functional materials for targeted cancer therapy are highlighted. The hope is that this review can inspire and guide those that are interested in the field of biomedicine to rationally design and develop new target‐based theranostic materials. 相似文献
67.
Caleb Acquah Dominic Agyei Eugene Marfo Obeng Sharadwata Pan Kei Xian Tan Michael Kobina Danquah 《Critical reviews in food science and nutrition》2020,60(7):1195-1206
AbstractThe food and health applications of bioactive peptides have grown remarkably in the past few decades. Current elucidations have shown that bioactive peptides have unique structural arrangement of amino acids, conferring distinct functionalities, and molecular affinity characteristics. However, whereas interest in the biological potency of bioactive peptides has grown, cost-effective techniques for monitoring the structural changes in these peptides and how these changes affect the biological properties have not grown at the same rate. Due to the high binding affinity of aptamers for other biomolecules, they have a huge potential for use in tracking the structural, conformational, and compositional changes in bioactive peptides. This review provides an overview of bioactive peptides and their essential structure–activity relationship. The review further highlights on the types and methods of synthesis of aptamers before the discussion of the prospects, merits, and challenges in the use of aptamers for bioaffinity interactions with bioactive peptides. 相似文献
68.
Yilong Liu Huimin Zhang Yahui Du Zhi Zhu Mingxia Zhang Zhehao Lv Lingling Wu Yuanyuan Yang Ao Li Liu Yang Yanling Song Sili Wang Chaoyong Yang 《Small (Weinheim an der Bergstrasse, Germany)》2020,16(20)
Minimal residual disease (MRD) offers a highly independent prognostic factor for leukemia patients. However, challenges confronting conventional MRD assays are high invasiveness, as well as limited detection sensitivity and clinical applicability. Inspired by the self‐adaptive skeleton and multiple suckers or tendrils of climbing plants, a biomimetic Multivalent Aptamer Nanoclimber (MANC)‐functionalized microfluidic chip (MANC‐Chip) is reported for minimally invasive, highly sensitive and clinically applicable MRD detection in the peripheral blood of T‐cell acute lymphoblastic leukemia patients. The MANCs are synthesized by a simple co‐polymerization reaction. Due to their flexible structure and cooperative multivalent effect, MANCs dramatically enhance the binding affinity of aptamers targeting leukemia cells. A deterministic lateral displacement‐patterned microfluidic chip is designed to further increase the collision probability between MANCs and leukemia cells. Benefiting from the synergistic effect of multivalent binding and enhanced collision, a high capture efficiency of 92.2% for leukemia cells is achieved. Moreover, the captured leukemia cells can be released with high efficiency of 88.9% and high viability of 93.8% via nuclease treatment prior to downstream analysis. Overall, the excellent features of MANC‐Chip make it very useful for precise detection of MRD and better understanding of leukemia. 相似文献
69.
Exosomes are a novel and promising drug delivery platform because of their endogenous origin, stability, biocompatibility, and other unique features. As the efficient loading and delivery of long RNA to target cells for therapeutic purposes remains challenging, a new exosome‐based RNA delivery system is proposed using a controllable RNA enrichment and releasing protocol. The system employs RNA aptamer–protein interactions and reversible light‐inducible protein–protein interaction modules by remolding exosome producer cells. Endogenous microRNA 21 (miR‐21) sponges, inhibitors of miR‐21, are successfully enriched on the plasma membrane and are sorted into exosomes by the biogenesis of the exosomes. The loading capacity of miR‐21 sponges is enhanced by 14‐fold in the light‐inducible loading system. In addition, targeted delivery of miR‐21 to leukemia cells is achieved by modifying exosomes with the cholesterol‐conjugated aptamer AS1411, resulting in significant cell apoptosis by blocking the function of miR‐21 in leukemia cells. This work provides an exosome‐based light‐inducible vehicle to efficiently load and deliver long endogenous RNA, which can enable more RNA‐based therapeutics for personalized cancer medicine. 相似文献
70.