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排序方式: 共有70条查询结果,搜索用时 15 毫秒
1.
Serber Z Straub W Corsini L Nomura AM Shimba N Craik CS Ortiz de Montellano P Dötsch V 《Journal of the American Chemical Society》2004,126(22):7119-7125
Studying protein components of large intracellular complexes by in-cell NMR has so far been impossible because the backbone resonances are unobservable due to their slow tumbling rates. We describe a methodology that overcomes this difficulty through selective labeling of methyl groups, which possess more favorable relaxation behavior. Comparison of different in-cell labeling schemes with three different proteins, calmodulin, NmerA, and FKBP, shows that selective labeling with [(13)C]methyl groups on methionine and alanine provides excellent sensitivity with low background levels at very low costs. 相似文献
2.
Dr. Christina I. Schroeder Dr. Lachlan D. Rash Xavier Vila‐Farrés Dr. K. Johan Rosengren Dr. Mehdi Mobli Prof. Glenn F. King Prof. Paul F. Alewood Prof. David J. Craik Dr. Thomas Durek 《Angewandte Chemie (International ed. in English)》2014,53(4):1017-1020
Mambalgins are a novel class of snake venom components that exert potent analgesic effects mediated through the inhibition of acid‐sensing ion channels (ASICs). The 57‐residue polypeptide mambalgin‐2 (Ma‐2) was synthesized by using a combination of solid‐phase peptide synthesis and native chemical ligation. The structure of the synthetic toxin, determined using homonuclear NMR, revealed an unusual three‐finger toxin fold reminiscent of functionally unrelated snake toxins. Electrophysiological analysis of Ma‐2 on wild‐type and mutant ASIC1a receptors allowed us to identify α‐helix 5, which borders on the functionally critical acidic pocket of the channel, as a major part of the Ma‐2 binding site. This region is also crucial for the interaction of ASIC1a with the spider toxin PcTx1, thus suggesting that the binding sites for these toxins substantially overlap. This work lays the foundation for structure–activity relationship (SAR) studies and further development of this promising analgesic peptide. 相似文献
3.
Racemic and Quasi‐Racemic X‐ray Structures of Cyclic Disulfide‐Rich Peptide Drug Scaffolds 下载免费PDF全文
Conan K. Wang Gordon J. King Susan E. Northfield Paola G. Ojeda Prof. Dr. David J. Craik 《Angewandte Chemie (International ed. in English)》2014,53(42):11236-11241
Cyclic disulfide‐rich peptides have exceptional stability and are promising frameworks for drug design. We were interested in obtaining X‐ray structures of these peptides to assist in drug design applications, but disulfide‐rich peptides can be notoriously difficult to crystallize. To overcome this limitation, we chemically synthesized the L ‐ and D ‐forms of three prototypic cyclic disulfide‐rich peptides: SFTI‐1 (14‐mer with one disulfide bond), cVc1.1 (22‐mer with two disulfide bonds), and kB1 (29‐mer with three disulfide bonds) for racemic crystallization studies. Facile crystal formation occurred from a racemic mixture of each peptide, giving structures solved at resolutions from 1.25 Å to 1.9 Å. Additionally, we obtained the quasi‐racemic structures of two mutants of kB1, [G6A]kB1, and [V25A]kB1, which were solved at a resolution of 1.25 Å and 2.3 Å, respectively. The racemic crystallography approach appears to have broad utility in the structural biology of cyclic peptides. 相似文献
4.
Plínio C. Sathler Charles S. Craik Toshihiko Takeuchi Russolina B. Zingali Helena C. Castro 《Applied biochemistry and biotechnology》2010,160(8):2355-2365
Ecotin is a bidentate, fold-specific inhibitor of mammalian serine-proteases produced by Escherichia coli. This molecule may be engineered to increase and/or change its affinity and specificity providing significant biotechnological
potential. Since ecotin binds tightly to serine proteases of the trypsin fold, it may help to identify the role of these enzymes
in different biological processes. In this work, we tested ecotin variants as an affinity purification reagent for identifying
enzymes in samples of tumor progression and mammary gland involution. Initially, we used a commercial source of urokinase-type
plasminogen activator (u-PA) that remained fully active after elution from an affinity column of the ecotin variant (M84R,
M85R). We then successfully identified u-PA from more complex mixtures including lysates from a prostate cancer cell line
and involuting mouse mammary glands. Interestingly, a membrane-type serine protease 1 was isolated from the Triton X-100-solubilized
PC-3 cell lysates, and surprisingly, haptoglobin, a serine-protease homolog protein, was also identified in mammary gland
lysates and in blood. Haptoglobin does not prevent ecotin inhibition of u-PA, but it may act as a carrier within blood when
ecotin is used in vivo. Finally, this affinity purification matrix was also able to identify a thrombin-like enzyme from snake venom using an ecotin
variant directed against thrombin. Overall, the ecotin variants acted as robust tools for the isolation and characterization
of proteins with a trypsin fold. Thus, they may assist in the understanding of the role of these serine proteases and homologous
proteins in different biological processes. 相似文献
5.
R.J.M. Craik 《Applied Acoustics》1982,15(4):275-282
Conventional methods for determining the properties of building materials by the measurement of the longitudinal wavespeed suffer from the disadvantage that the measurements can only be carried out in localised parts of the building, usually through the thickness of the wall. The techniques, although non-destructive, may mark decorative finishes.Similar methods have been used to obtain the wavespeed from low frequency pulses which may be used in all parts of the structure without damage. The technique is very simple and the results are accurate. The simplicity of the technique makes the method suitable for many applications. 相似文献
6.
D.J. Craik 《Physics letters. A》1983,96(6):283-285
The finite-difference Laplace equation applying at a magnetic interface has been derived by Binns and Lawrenson using the rather difficult concept of “fictitious potential”. The equation may be verified by recourse to a simple model, and this model may further be used to give an alternative and somewhat clearer derivation. 相似文献
7.
It has recently been shown that for situations in which two rooms are connected by a ventilation duct, the principal acoustic path from one room to the adjacent room is that via the duct cavity. As existing theories were found to be inadequate in predicting this path noise reduction, experiments have been carried out to determine the values of the unknown variables. These are described and a design guide for determining the overall noise reduction of the system has been produced. 相似文献
8.
Huawu Yin David J. Craik Conan K. Wang 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(23):7734-7738
Loops at protein–protein interfaces are a rich source of peptide leads that have high specificity and low toxicity. Although such peptides typically need to be constrained to overcome thermodynamic and metabolic limitations, design guidelines to obtain a successfully constrained peptides, and thus facilitate the transition from loop to drug, are relatively poorly formulated. In this work, we surveyed the structures of interface loops and found the position of the terminal residues to be a key determinant of conformation. We used this knowledge to improve the process of molecular grafting, a valuable approach for constraining and stabilising peptides by fusing them to a suitable scaffold. We show that an informed choice of where a loop is “anchored” to a scaffold improves its form and function. This knowledge can help guide the choice of loop and its matching scaffold, and thus increase the success rate for designing stable and potent peptide drug leads. 相似文献
9.
Structure–Activity Studies of Cysteine‐Rich α‐Conotoxins that Inhibit High‐Voltage‐Activated Calcium Channels via GABAB Receptor Activation Reveal a Minimal Functional Motif 下载免费PDF全文
Dr. Bodil B. Carstens Dr. Géza Berecki James T. Daniel Han Siean Lee Kathryn A. V. Jackson Dr. Han‐Shen Tae Dr. Mahsa Sadeghi Dr. Joel Castro Tracy O'Donnell Dr. Annemie Deiteren Prof. Stuart M. Brierley Prof. David J. Craik Prof. David J. Adams Dr. Richard J. Clark 《Angewandte Chemie (International ed. in English)》2016,55(15):4692-4696
α‐Conotoxins are disulfide‐rich peptides that target nicotinic acetylcholine receptors. Recently we identified several α‐conotoxins that also modulate voltage‐gated calcium channels by acting as G protein‐coupled GABAB receptor (GABABR) agonists. These α‐conotoxins are promising drug leads for the treatment of chronic pain. To elucidate the diversity of α‐conotoxins that act through this mechanism, we synthesized and characterized a set of peptides with homology to α‐conotoxins known to inhibit high voltage‐activated calcium channels via GABABR activation. Remarkably, all disulfide isomers of the active α‐conotoxins Pu1.2 and Pn1.2, and the previously studied Vc1.1 showed similar levels of biological activity. Structure determination by NMR spectroscopy helped us identify a simplified biologically active eight residue peptide motif containing a single disulfide bond that is an excellent lead molecule for developing a new generation of analgesic peptide drugs. 相似文献
10.
D. P. L. Aude Craik N. M. Linke T. P. Harty C. J. Ballance D. M. Lucas A. M. Steane D. T. C. Allcock 《Applied physics. B, Lasers and optics》2014,114(1-2):3-10
We propose a surface ion trap design incorporating microwave control electrodes for near-field single-qubit control. The electrodes are arranged so as to provide arbitrary frequency, amplitude and polarization control of the microwave field in one trap zone, whilst a similar set of electrodes is used to null the residual microwave field in a neighbouring zone. The geometry is chosen to reduce the residual field to the 0.5 % level without nulling fields; with nulling, the crosstalk may be kept close to the 0.01 % level for realistic microwave amplitude and phase drift. Using standard photolithography and electroplating techniques, we have fabricated a proof-of-principle electrode array with two trapping zones. We discuss requirements for the microwave drive system and prospects for scalability to a large 2-D trap array. 相似文献