全文获取类型
收费全文 | 449篇 |
免费 | 45篇 |
出版年
2023年 | 2篇 |
2022年 | 4篇 |
2021年 | 4篇 |
2020年 | 4篇 |
2019年 | 11篇 |
2018年 | 5篇 |
2017年 | 9篇 |
2016年 | 14篇 |
2015年 | 17篇 |
2014年 | 15篇 |
2013年 | 26篇 |
2012年 | 22篇 |
2011年 | 19篇 |
2010年 | 22篇 |
2009年 | 12篇 |
2008年 | 34篇 |
2007年 | 28篇 |
2006年 | 24篇 |
2005年 | 31篇 |
2004年 | 20篇 |
2003年 | 17篇 |
2002年 | 13篇 |
2001年 | 11篇 |
2000年 | 13篇 |
1999年 | 19篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1993年 | 7篇 |
1992年 | 9篇 |
1991年 | 6篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 8篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1982年 | 3篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1975年 | 5篇 |
1974年 | 2篇 |
1973年 | 4篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1968年 | 2篇 |
1967年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有494条查询结果,搜索用时 15 毫秒
261.
The contryphan family of cyclic peptides, isolated recently from various species of cone shell, has the conserved sequence motif NH(3)(+)-X(1)COD-WX(5)PWC-NH(2), where X(1) is either Gly or absent, O is 4-trans-hydroxyproline, and X(5) is Glu, Asp, or Gln. The solution structures described herein of two new naturally occurring contryphan sequences, contryphan-Sm and des[Gly1]-contryphan-R, are similar to those of contryphan-R, the structure of which has been determined recently [Pallaghy et al. (1999) Biochemistry 38, 11553-11559]. The (1)H NMR chemical shifts of another naturally occurring peptide, contryphan-P, indicate that it also adopts a similar structure. All of these contryphans exist in solution as a mixture of two conformers due to cis-trans isomerization about the Cys2-Hyp3 peptide bond. The lower cis-trans ratio for contryphan-Sm enabled elucidation of the 3D structure of both its major and its minor forms, for which the patterns of (3)J(H)(alpha)(HN) coupling constants are very different. As with contryphan-R, the structure of the major form of contryphan-Sm (cis Cys2-Hyp3 peptide bond) contains an N-terminal chain reversal and a C-terminal type I beta-turn. The minor conformer (trans peptide bond) forms a hairpin structure with sheetlike hydrogen bonds and a type II beta-turn, with the D-Trp4 at the 'Gly position' of the turn. The ratio of conformers arising from cis-trans isomerism around the peptide bond preceding Hyp3 is sensitive to both the amino acid sequence and the solution conditions, varying from 2.7:1 to 17:1 across the five sequences. The sequence and structural determinants of the cis-trans isomerism have been elucidated by comparison of the cis-trans ratios for these peptides with those for contryphan-R and an N-acetylated derivative thereof. The cis-trans ratio is reduced for peptides in which either the charged N-terminal ammonium or the X(5) side-chain carboxylate is neutralized, implying that an electrostatic interaction between these groups stabilizes the cis conformer relative to the trans. These results on the structures and cis-trans equilibrium of different conformers suggest a paradigm of 'locally determined but globally selected' folding for cyclic peptides and constrained protein loops, where the series of stereochemical centers in the loop dictates the favorable conformations and the equilibrium is determined by a small number of side-chain interactions. 相似文献
262.
Costa ET Olivera DS Meyer DA Ferreira VM Soto EE Frausto S Savage DD Browning MD Valenzuela CF 《The Journal of biological chemistry》2000,275(49):38268-38274
The actions of ethanol on brain ligand-gated ion channels have important roles in the pathophysiology of alcohol-related neurodevelopmental disorders and fetal alcohol syndrome. Studies have shown that N-methyl-d-aspartate (NMDA) receptors are among the ligand-gated ion channels affected by prenatal ethanol exposure. We exposed pregnant dams to an ethanol-containing liquid diet that results in blood ethanol levels near the legal intoxication limit in most states (0.08%). Primary cultures of hippocampal neurons were prepared from the neonatal offspring of these dams, and NMDA receptor function was assessed by patch clamp electrophysiological techniques after 6-7 days in culture in ethanol-free media. Unexpectedly, we did not detect any changes in hippocampal NMDA receptor function at either the whole-cell or single-channel levels. However, we determined that fetal alcohol exposure alters the actions of the neurosteroids pregnenolone sulfate and pregnenolone hemisuccinate, which potentiate NMDA receptor function. Western immunoblot analyses demonstrated that this alteration is not due to a change in the expression levels of NMDA receptor subunits. Importantly, in utero ethanol exposure did not affect the actions of neurosteroids that inhibit NMDA receptor function. Moreover, the actions of pregnenolone sulfate on type A gamma-aminobutyric acid and non-NMDA receptor function were unaltered by ethanol exposure in utero, which suggests that the alteration is specific to NMDA receptors. These findings are significant because they provide, at least in part, a plausible mechanistic explanation for the alterations in the behavioral responses to neurosteroids found in neonatal rats prenatally exposed to ethanol and to other forms of maternal stress (Zimmerberg, B., and McDonald, B. C. (1996) Pharmacol. Biochem. Behav. 55, 541-547). 相似文献
263.
264.
Signal recognition particle-dependent inner membrane targeting of the PulG Pseudopilin component of a type II secretion system
下载免费PDF全文
![点击此处可从《Journal of bacteriology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Francetic O Buddelmeijer N Lewenza S Kumamoto CA Pugsley AP 《Journal of bacteriology》2007,189(5):1783-1793
The pseudopilin PulG is an essential component of the pullulanase-specific type II secretion system from Klebsiella oxytoca. PulG is the major subunit of a short, thin-filament pseudopilus, which presumably elongates and retracts in the periplasm, acting as a dynamic piston to promote pullulanase secretion. It has a signal sequence-like N-terminal segment that, according to studies with green and red fluorescent protein chimeras, anchors unassembled PulG in the inner membrane. We analyzed the early steps of PulG inner membrane targeting and insertion in Escherichia coli derivatives defective in different protein targeting and export factors. The beta-galactosidase activity in strains producing a PulG-LacZ hybrid protein increased substantially when the dsbA, dsbB, or all sec genes tested except secB were compromised by mutations. To facilitate analysis of native PulG membrane insertion, a leader peptidase cleavage site was engineered downstream from the N-terminal transmembrane segment (PrePulG*). Unprocessed PrePulG* was detected in strains carrying mutations in secA, secY, secE, and secD genes, including some novel alleles of secY and secD. Furthermore, depletion of the Ffh component of the signal recognition particle (SRP) completely abolished PrePulG* processing, without affecting the Sec-dependent export of periplasmic MalE and RbsB proteins. Thus, PulG is cotranslationally targeted to the inner membrane Sec translocase by SRP. 相似文献
265.
The loss of function of PhaC1 is a survival mechanism that counteracts the stress caused by the overproduction of poly‐3‐hydroxyalkanoates in Pseudomonas putidaΔfadBA
下载免费PDF全文
![点击此处可从《Environmental microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
José I. Obeso Beatriz Maestro Jesús M. Sanz Elías R. Olivera José M. Luengo 《Environmental microbiology》2015,17(9):3182-3194
The poly‐3‐hydroxylkanoate (PHA)‐overproducing mutant Pseudomonas putida U ΔfadBA (PpΔfadBA) lacks the genes encoding the main β‐oxidation pathway (FadBA). This strain accumulates enormous amounts of bioplastics when cultured in chemically defined media containing PHA precursors (different n‐alkanoic or n‐aryl‐alkanoic acids) and an additional carbon source. In medium containing glucose or 4‐hydroxy‐phenylacetate, the mutant does not accumulate PHAs and grows just as the wild type (P. putida U). However, when the carbon source is octanoate, growth is severely impaired, suggesting that in PpΔfadBA, the metabolic imbalance resulting from a lower rate of β‐oxidation, together with the accumulation of bioplastics, causes severe physiological stress. Here, we show that PpΔfadBA efficiently counteracts this latter effect via a survival mechanism involving the introduction of spontaneous mutations that block PHA accumulation. Surprisingly, genetic analyses of the whole pha cluster revealed that these mutations occurred only in the gene encoding one of the polymerases (phaC1) and that the loss of PhaC1 function was enough to prevent PHA synthesis. The influence of these mutations on the structure of PhaC1 and the existence of a protein–protein (PhaC1–PhaC2) interaction that explains the functionality of the polymerization system are discussed herein. 相似文献
266.
Stamenković Olivera Stojković Piperac Milica Milošević Djuradj Buzhdygan Oksana Y. Petrović Ana Jenačković Dragana Đurđević Aca Čerba Dubravka Vlaičević Barbara Nikolić Danijela Simić Vladica 《Hydrobiologia》2019,832(1):65-84
Hydrobiologia - Identifying the evolutionary and developmental bases of adaptive phenotypes is of central interest in evolutionary biology. Cichlid fishes have been a useful research model due to... 相似文献
267.
Aguilar MB López-Vera E Heimer de la Cotera EP Falcón A Olivera BM Maillo M 《Peptides》2007,28(1):18-23
Peptide sr11a was purified from the venom of Conus spurius, a vermivorous cone snail collected in the Yucatan Channel, in the Western Atlantic. Its primary structure was determined by automatic Edman degradation after reduction and alkylation. Its molecular mass, as determined by MALDI-TOF mass spectrometry (average mass 3650.77 Da), confirmed the chemical data (calculated average mass, 3651.13 Da). The sequence of peptide sr11a (CRTEGMSCgamma gamma NQQCCWRSCCRGECEAPCRFGP&; gamma, gamma-carboxy-Glu; &, amidated C-terminus) shows eight Cys residues arranged in the pattern that defines the I-superfamily of conotoxins. Peptide sr11a contains two gamma-carboxy-Glu residues, a post-translational modification that has been found in other I-conotoxins from species that live in the West Pacific: r11e from the piscivorous Conus radiatus, and kappa-BtX from the vermivorous Conus betulinus. Peptide sr11a is the eighth I-conotoxin isolated from a Conus venom and the first I-conotoxin from a species from the Western Atlantic. Peptide sr11a produced stiffening of body, limbs and tail when injected intracranially into mice. 相似文献
268.
Oligoryzomys flavescens, a common rodent of the temperate regions of South America, has been identified as a Hantavirus reservoir. There is still little information concerning its reproductive biology, which is essential to devise effective control measurement of natural populations. This rodent is a seasonal breeder and adult males exhibit a short period of testicular regression during winter months (June-August). In the present study we provided a histological and ultrastructural analysis of the composition of the testis of sexually mature O. flavescens during the breeding season. Over 95% of the testicular parenchyma was occupied by the seminiferous tubules and less than 5% by the interstitial tissue. The mean tubular diameter and epithelium height were 147.2 and 57.8 microm, respectively. The spermatogenic wave was characterized and eight spermatogenesis stages were identified according to the tubular morphology method. Their length, estimated as their relative frequencies, were (I-VIII) 8.8, 14.9, 4.0, 5.0, 10.4, 5.8, 27.0, and 23.9. Ultrastructural features of spermiogenesis are shown for the first time in a sigmodontine rodent. 相似文献
269.