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51.
Jang S Sreerama N Liao VH Lu SH Li FY Shin S Woody RW Lin SH 《Protein science : a publication of the Protein Society》2006,15(10):2290-2299
A computational model was developed to examine the phototriggered folding of a caged protein, a protein modified with an organic photolabile cross-linker. Molecular dynamics simulations of the modified 36-residue fragment of subdomain B of chicken villin head piece with a photolabile linker were performed, starting from both the caged and the uncaged structures. Construction of a free-energy landscape, based on principal components as well as on radius of gyration versus root-mean-square deviation, and circular dichroism calculations were employed to characterize folding behavior and structures. The folded structures observed in the molecular dynamics trajectories were found to be similar to that of the wild-type protein, in agreement with the published experimental results. The free-energy landscapes of the modified and wild-type proteins have similar topology, suggesting common thermodynamic/kinetic behavior. The existence of small differences in the free-energy surface of the modified protein from that of the native protein, however, indicates subtle differences in the folding behavior. 相似文献
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Latkany P Duggal M Goulet J Paek H Rambo M Palmisano P Levin W Erdos J Justice A Brandt C 《Journal of ocular biology, diseases, and informatics》2010,3(1):30-34
We performed a validation study by chart review of data for exudative age-related macular degeneration (eAMD) and, because of the Veterans Administration (VA) therapy policy, ranibizumab usage in the largest electronic medical record system in the USA. We reviewed 5,854 distinct patients who visited an ophthalmology clinic within VA Connecticut from January 2006-December 2008. We randomly selected 98 of 138 distinct eAMD patients and 265 of 5,588 non-eAMD patients who did not receive ranibizumab. International Classification of Diseases, Ninth Revision, Clinical Modification coding of eAMD had an excellent positive predictive value of 97.8% (95% confidence interval (CI), 93.5-99.4%). The national Decision Support System (DSS) had an excellent positive predictive value of 100% (95% CI, 79.9-100%) for ranibizumab. However, the negative predictive value of the DSS dispensed ranibizumab decreased to 67.5 (95% CI, 62.1-72.4) because of a change in the way local values were stored that led to errors. Therefore, validation of clinical information over time in large databases is necessary. 相似文献
54.
Clark LA Boriack-Sjodin PA Eldredge J Fitch C Friedman B Hanf KJ Jarpe M Liparoto SF Li Y Lugovskoy A Miller S Rushe M Sherman W Simon K Van Vlijmen H 《Protein science : a publication of the Protein Society》2006,15(5):949-960
Improving the affinity of a high-affinity protein-protein interaction is a challenging problem that has practical applications in the development of therapeutic biomolecules. We used a combination of structure-based computational methods to optimize the binding affinity of an antibody fragment to the I-domain of the integrin VLA1. Despite the already high affinity of the antibody (Kd approximately 7 nM) and the moderate resolution (2.8 A) of the starting crystal structure, the affinity was increased by an order of magnitude primarily through a decrease in the dissociation rate. We determined the crystal structure of a high-affinity quadruple mutant complex at 2.2 A. The structure shows that the design makes the predicted contacts. Structural evidence and mutagenesis experiments that probe a hydrogen bond network illustrate the importance of satisfying hydrogen bonding requirements while seeking higher-affinity mutations. The large and diverse set of interface mutations allowed refinement of the mutant binding affinity prediction protocol and improvement of the single-mutant success rate. Our results indicate that structure-based computational design can be successfully applied to further improve the binding of high-affinity antibodies. 相似文献
55.
Goring DR Banks P Fallis L Baszczynski CL Beversdorf WD Rothstein SJ 《The Plant journal : for cell and molecular biology》1992,2(6):999-1003
We have previously described a developmentally regulated mRNA in maize that accumulates in mature embryos and is involved in a variety of stress responses in the plant. The sequence of the encoded 16 kDa protein (MA16) predicts that it is an RNA-binding protein, since it possesses a ribonucleoprotein consensus sequence-type RNA-binding domain (CS-RBD). To assess the predicted RNA binding property of the protein and as a starting point to characterize its function we have used ribohomopolymer-binding assays. Here we show that the MA16-encoded protein binds preferentially to uridine- and guanosine-rich RNAs. In light of these results a likely role for this protein in RNA metabolism during late embryogenesis and in the stress response is discussed. 相似文献
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Control of estrus in dairy heifers with Syncro-Mate-B was evaluated in five experiments with a total of 393 Holstein heifers. Estradiol-17β at implant removal or gonadotropin releasing hormone 40 hr after implant removal did not cause any beneficial effect on fertility. In heifers implanted on selected days of the estrous cycle, 88.3% of heifers treated with SMB only were in estrus within 5 days of implant removal and fertility was not significantly different from that of control heifers. In heifers implanted at random stages of the estrous cycle, estrus occurred within 5 days of implant removal in 88.7% of 159 SMB treated heifers. First service conception rates (heifers pregnant of heifers inseminated) and pregnancy rates (heifers pregnant of heifers assigned) were 72.7% and 60.8% for heifers inseminated 8 to 16 hr after estrus within 5 days of implant removal, 55.0% and 55.0% for heifers inseminated 48 hr after implant removal without regard to estrus and 71.6% and 67.1% for control heifers inseminated over a 25 day period. 相似文献
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The folding mechanism of pectate lyase C (pelC) involves two slow phases that have been attributed to proline isomerization. To have a more detailed and complete understanding of the folding mechanism, experiments have been carried out to identify the prolyl-peptide bonds responsible for the slow kinetics. Site-directed mutagenesis has been used to mutate each of the prolines in pelC to alanine or valine. It has been determined that isomerization of the Leu219-Pro220 peptide bond is responsible for the slowest folding phase observed. The mutant P220A shows kinetic behavior that is identical to the wild-type protein except that the 46-s phase is eliminated. The Leu219-Pro220 peptide bond is cis in the native enzyme. An analysis of the free energy of unfolding of this mutant indicates that the mutation destabilizes the protein by about 4 kcal/mol. However, it appears that the major refolding pathways are unaltered. Further mutations were carried out in order to assign the peptide bond responsible for the 21-s folding phase in pelC. Mutation of the remaining 11 prolines, which are trans in the native enzyme, resulted in no significant changes in the kinetic folding behavior. The conclusion from these experiments is that the 21-s phase involves isomerization of more than one prolyl-peptide bond with similar activation energies. 相似文献
60.
Estimation of the number of alpha-helical and beta-strand segments in proteins using circular dichroism spectroscopy 下载免费PDF全文
Sreerama N Venyaminov SY Woody RW 《Protein science : a publication of the Protein Society》1999,8(2):370-380
A simple approach to estimate the number of alpha-helical and beta-strand segments from protein circular dichroism spectra is described. The alpha-helix and beta-sheet conformations in globular protein structures, assigned by DSSP and STRIDE algorithms, were divided into regular and distorted fractions by considering a certain number of terminal residues in a given alpha-helix or beta-strand segment to be distorted. The resulting secondary structure fractions for 29 reference proteins were used in the analyses of circular dichroism spectra by the SELCON method. From the performance indices of the analyses, we determined that, on an average, four residues per alpha-helix and two residues per beta-strand may be considered distorted in proteins. The number of alpha-helical and beta-strand segments and their average length in a given protein were estimated from the fraction of distorted alpha-helix and beta-strand conformations determined from the analysis of circular dichroism spectra. The statistical test for the reference protein set shows the high reliability of such a classification of protein secondary structure. The method was used to analyze the circular dichroism spectra of four additional proteins and the predicted structural characteristics agree with the crystal structure data. 相似文献