全文获取类型
收费全文 | 128篇 |
免费 | 10篇 |
国内免费 | 4篇 |
出版年
2022年 | 3篇 |
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 5篇 |
2017年 | 1篇 |
2016年 | 6篇 |
2015年 | 11篇 |
2014年 | 12篇 |
2013年 | 3篇 |
2012年 | 4篇 |
2011年 | 3篇 |
2010年 | 6篇 |
2009年 | 6篇 |
2008年 | 6篇 |
2007年 | 3篇 |
2006年 | 7篇 |
2005年 | 8篇 |
2004年 | 4篇 |
2003年 | 3篇 |
2002年 | 3篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 1篇 |
1998年 | 6篇 |
1997年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 6篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1983年 | 4篇 |
1978年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有142条查询结果,搜索用时 31 毫秒
1.
The way a protein responds to mutation provides key insights into its architecture and energetics. Mutations are improving the understanding both of protein folding and stability, and of the adaptability of the hydrophobic core. The importance of intermolecular effects in crystal structures is being emphasized and new insights into the correspondence between crystal and solution structures are being developed. 相似文献
2.
Comparison of the intermediate complexes of human growth hormone bound to the human growth hormone and prolactin receptors. 总被引:4,自引:2,他引:2
下载免费PDF全文
![点击此处可从《Protein science : a publication of the Protein Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A. A. Kossiakoff W. Somers M. Ultsch K. Andow Y. A. Muller A. M. De Vos 《Protein science : a publication of the Protein Society》1994,3(10):1697-1705
The crystal structures of complexes of human growth hormone (hGH) with the growth hormone and prolactin receptors (hGHR and hPRLR, respectively), together with the mutational data available for these systems, suggest that an extraordinary combination of conformational adaptability, together with finely tuned specificity, governs the molecular recognition processes operative in these systems. On the one hand, in the active 1:2 ligand-receptor complexes, 2 copies of the same receptor use the identical set of binding determinants to recognize topographically different surfaces on the hormone. On the other hand, comparing the 1:1 hGH-hGHR and hGH-hPRLR complexes, 2 distinct receptors use this same set of binding determinants to interact with the identical binding site on the ligand, even though few residues among the binding determinants are conserved. The structural evidence demonstrates that this versatility is accomplished by local conformational flexibility of the binding loops, allowing adaptation to different binding environments, together with rigid-body movements of the receptor domains, necessary for the creation of specific interactions with the same binding site. 相似文献
3.
Nielsen J; Peixoto AA; Piccin A; Costa R; Kyriacou CP; Chalmers D 《Molecular biology and evolution》1994,11(6):839-853
The region of the clock gene period (per) that encodes a repetitive tract
of threonine-glycine (Thr-Gly) pairs has been compared between Dipteran
species both within and outside the Drosophilidae. All the non-
Drosophilidae sequences in this region are short and present a remarkably
stable picture compared to the Drosophilidae, in which the region is much
larger and extremely variable, both in size and composition. The
accelerated evolution in the repetitive region of the Drosophilidae appears
to be mainly due to an expansion of two ancestral repeats, one encoding a
Thr-Gly dipeptide and the other a pentapeptide rich in serine, glycine, and
asparagine or threonine. In some drosophilids the expansion involves a
duplication of the pentapeptide sequence, but in Drosophila pseudoobscura
both the dipeptide and the pentapeptide repeats are present in larger
numbers. In the nondrosophilids, however, the pentapeptide sequence is
represented by one copy and the dipeptide by two copies. These observations
fulfill some of the predictions of recent theoretical models that have
simulated the evolution of repetitive sequences.
相似文献
4.
Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with altered specificities. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Protein science : a publication of the Protein Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A. J. Scheidig T. R. Hynes L. A. Pelletier J. A. Wells A. A. Kossiakoff 《Protein science : a publication of the Protein Society》1997,6(9):1806-1824
The crystal structures of the inhibitor domain of Alzheimer's amyloid beta-protein precursor (APPI) complexed to bovine chymotrypsin (C-APPI) and trypsin (T-APPI) and basic pancreatic trypsin inhibitor (BPTI) bound to chymotrypsin (C-BPTI) have been solved and analyzed at 2.1 A, 1.8 A, and 2.6 A resolution, respectively. APPI and BPTI belong to the Kunitz family of inhibitors, which is characterized by a distinctive tertiary fold with three conserved disulfide bonds. At the specificity-determining site of these inhibitors (P1), residue 15(I)4 is an arginine in APPI and a lysine in BPTI, residue types that are counter to the chymotryptic hydrophobic specificity. In the chymotrypsin complexes, the Arg and Lys P1 side chains of the inhibitors adopt conformations that bend away from the bottom of the binding pocket to interact productively with elements of the binding pocket other than those observed for specificity-matched P1 side chains. The stereochemistry of the nucleophilic hydroxyl of Ser 195 in chymotrypsin relative to the scissile P1 bond of the inhibitors is identical to that observed for these groups in the trypsin-APPI complex, where Arg 15(I) is an optimal side chain for tryptic specificity. To further evaluate the diversity of sequences that can be accommodated by one of these inhibitors, APPI, we used phage display to randomly mutate residues 11, 13, 15, 17, and 19, which are major binding determinants. Inhibitors variants were selected that bound to either trypsin or chymotrypsin. As expected, trypsin specificity was principally directed by having a basic side chain at P1 (position 15); however, the P1 residues that were selected for chymotrypsin binding were His and Asn, rather than the expected large hydrophobic types. This can be rationalized by modeling these hydrophilic side chains to have similar H-bonding interactions to those observed in the structures of the described complexes. The specificity, or lack thereof, for the other individual subsites is discussed in the context of the "allowed" residues determined from a phage display mutagenesis selection experiment. 相似文献
5.
Evolutionary origin of human and primate malarias: evidence from the circumsporozoite protein gene 总被引:8,自引:1,他引:7
We have analyzed the conserved regions of the gene coding for the
circumsporozoite protein (CSP) in 12 species of Plasmodium, the malaria
parasite. The closest evolutionary relative of P. falciparum, the agent of
malignant human malaria, is P. reichenowi, a chimpanzee parasite. This is
consistent with the hypothesis that P. falciparum is an ancient human
parasite, associated with humans since the divergence of the hominids from
their closest hominoid relatives. Three other human Plasmodium species are
each genetically indistinguishable from species parasitic to nonhuman
primates; that is, for the DNA sequences included in our analysis, the
differences between species are not greater than the differences between
strains of the human species. The human P. malariae is indistinguishable
from P. brasilianum, and P. vivax is indistinguishable from P. simium; P.
brasilianum and P. simium are parasitic to New World monkeys. The human P.
vivax-like is indistinguishable from P. simiovale, a parasite of Old World
macaques. We conjecture that P. malariae, P. vivax, and P. vivax-like are
evolutionarily recent human parasites, the first two at least acquired only
within the last several thousand years, and perhaps within the last few
hundred years, after the expansion of human populations in South America
following the European colonizations. We estimate the rate of evolution of
the conserved regions of the CSP gene as 2.46 x 10(-9) per site per year.
The divergence between the P. falciparum and P. reichenowi lineages is
accordingly dated 8.9 Myr ago. The divergence between the three lineages
leading to the human parasites is very ancient, about 100 Myr old between
P. malariae and P. vivax (and P. vivax-like) and about 165 Myr old between
P. falciparum and the other two.
相似文献
6.
Photosynthetic enhancement studies performed at 619 nm (excitation of Systems I and II) and at 446 nm (mainly excitation of System I) revealed an 18% photosynthetic enhancement simultaneously with a 31% reduction in glycolate excretion. This observation supports the hypothesis that some glycolate may be consumed in an oxidation process associated with System I when System II is poorly excited and the supply of electrons from the water splitting process of photosynthesis is low. 相似文献
7.
Engineering subtilisin and its substrates for efficient ligation of peptide bonds in aqueous solution 总被引:9,自引:0,他引:9
Protein engineering techniques were used to construct a derivative of the serine protease subtilisin that ligates peptides efficiently in water. The subtilisin double mutant in which the catalytic Ser221 was converted to Cys (S221C) and Pro225 converted to Ala (P225A) has 10-fold higher peptide ligase activity and at least 100-fold lower amidase activity than the singly mutated thiolsubtilisin (S221C) that was previously shown to have some peptide ligase activity [Nakatsuka, T., Sasaki, T., & Kaiser, E.T. (1987) J. Am. Chem. Soc. 109, 3808-3810]. A 1.5-A X-ray crystal structure of an oxidized derivative of the double mutant (S221C/P225A) supports the protein design strategy in showing that the P225A mutation partly relieves the steric crowding expected from the S221C substitution, thus accounting for its improved catalytic efficiency. Stable and synthetically reasonable alkyl ester peptide substrates were prepared that rapidly acylate the S221C/P225A enzyme, and aminolysis of the resulting thioacyl-enzyme intermediate by various peptides is strongly preferred over hydrolysis. The efficiency of aminolysis is relatively insensitive to the sequence of the first two residues in the acyl acceptor peptide whose alpha-amino group attacks the thioacyl-enzyme. To obtain greater flexibility in the choice of coupling sites, a set of three additional peptide ligases were engineered by introducing mutations into the parent ligase (S221C/P225A) that were previously shown to change the specificity of subtilisin for the residue nearest the acyl bond (the P1 residue). The specificity properties of the parent ligase and derivatives of it paralleled those of wild type and corresponding specificity variants.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
8.
X-ray crystal structure of the protease inhibitor domain of Alzheimer's amyloid beta-protein precursor 总被引:4,自引:0,他引:4
Alzheimer's amyloid beta-protein precursor contains a Kunitz protease inhibitor domain (APPI) potentially involved in proteolytic events leading to cerebral amyloid deposition. To facilitate the identification of the physiological target of the inhibitor, the crystal structure of APPI has been determined and refined to 1.5-A resolution. Sequences in the inhibitor-protease interface of the correct protease target will reflect the molecular details of the APPI structure. While the overall tertiary fold of APPI is very similar to that of the Kunitz inhibitor BPTI, a significant rearrangement occurs in the backbone conformation of one of the two protease binding loops. A number of Kunitz inhibitors have similar loop sequences, indicating the structural alteration is conserved and potentially an important determinant of inhibitor specificity. In a separate region of the protease binding loops, APPI side chains Met-17 and Phe-34 create an exposed hydrophobic surface in place of Arg-17 and Val-34 in BPTI. The restriction this change places on protease target sequences is seen when the structure of APPI is superimposed on BPTI complexed to serine proteases, where the hydrophobic surface of APPI faces a complementary group of nonpolar side chains on kallikrein A versus polar side chains on trypsin. 相似文献
9.
土壤中棉花黄萎病菌SYBR Green Ⅰ荧光RT-PCR定量检测技术研究 总被引:3,自引:0,他引:3
为实现田间土壤棉花黄萎病菌的早期检测,建立了土壤中棉花黄萎病菌的SYBR Green I荧光定量PCR检测方法。以含342bp PCR扩增产物的阳性质粒为参考,构建了标准曲线,并对该曲线的特异性、敏感性、可重复性进行了评价。结果表明,该方法具有快速、特异性强、敏感度高等特点。检测范围在3.8×103-3.8×108copies/μL之间有良好的线性关系,相关系数R2为0.996,扩增效率为101.5%,灵敏度比常规PCR方法高102倍。 相似文献
10.
The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide‐mediated vasorelaxation in BALB/c mice
下载免费PDF全文
![点击此处可从《Cell biochemistry and function》网站下载免费的PDF全文](/ch/ext_images/free.gif)
S Gohin A Carriero C Chenu AA Pitsillides TR Arnett M Marenzana 《Cell biochemistry and function》2016,34(2):52-62
There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L‐NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1–34] (80 µg/kg/day) or L‐NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro‐CT, histomorphometry and three‐point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co‐treatment with L‐NAME blocked the action of PTH on blood flow, whereas L‐NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co‐treatment with L‐NAME restricted the PTH‐stimulated increase in cortical bone formation but had no clear‐cut effects in trabecular bone. Co‐treatment with L‐NAME did not affect the mechanical strength in femurs induced by iPTH. These results suggest that NO‐mediated vasorelaxation plays partly a role in the anabolic action of PTH on cortical bone. © 2016 The Authors. Cell Biochemistry and Function published by John Wiley & Sons, Ltd. 相似文献