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101.
102.
Bhardwaj A Walker-Kopp N Wilkens S Cingolani G 《Protein science : a publication of the Protein Society》2008,17(9):1475-1485
A common objective in protein engineering is the enhancement of the thermodynamic properties of recombinant proteins for possible applications in nanobiotechnology. The performance of proteins can be improved by the rational design of chimeras that contain structural elements with the desired properties, thus resulting in a more effective exploitation of protein folds designed by nature. In this paper, we report the design and characterization of an ultra-stable self-refolding protein fiber, which rapidly reassembles in solution after denaturation induced by harsh chemical treatment or high temperature. This engineered protein fiber was constructed on the molecular framework of bacteriophage P22 tail needle gp26, by fusing its helical core to the foldon domain of phage T4 fibritin. Using protein engineering, we rationally permuted the foldon upstream and downstream from the gp26 helical core and characterized gp26-foldon chimeras by biophysical analysis. Our data demonstrate that one specific protein chimera containing the foldon immediately downstream from the gp26 helical core, gp26(1-140)-F, displays the highest thermodynamic and structural stability and refolds spontaneously in solution following denaturation. The gp26-foldon chimeric fiber remains stable in 6.0 M guanidine hydrochloride, or at 80 degrees C, rapidly refolds after denaturation, and has both N and C termini accessible for chemical/biological modification, thereby representing an ideal platform for the design of self-assembling nanoblocks. 相似文献
103.
The mt genome of Paa spinosa (Anura: Ranoidae) is a circular molecule of 18,012 bp in length, containing 38 genes (including an extra copy of tRNA-Met gene). This mt genome is characterized by three distinctive features: a cluster of rearranged tRNA genes (LTPF tRNA gene cluster), a tandem duplication of tRNA-Met gene (Met1 and Met2), and distinct repeat regions at both 5′ and 3′-sides in the control region. Comparing the locations and the sequences of all tRNA-Met genes among Ranoidae, and constructing NJ tree of the nucleotide of those tRNA-Met genes, we suggested a tandem duplication of tRNA-Met gene can be regarded as a synapomorphy of Dicroglossinae. To further investigate the phylogenetic relationships of anurans, phylogenetic analyses (BI, ML and MP) based on the nucleotide dataset and the corresponding amino acid dataset of 11 protein-coding genes (except ND5 and ATP8) arrived at the similar topology. 相似文献
104.
The temperature–frequency relationship in nerve conduction block induced by high-frequency, biphasic electrical current was
investigated by computer simulation using an amphibian myelinated axon model based on Frankenhaeuser–Huxley (FH) equations.
For an axon of diameter 10 μm, the minimal blocking frequency was changed from 6 to 3 kHz as the temperature was decreased
from 37°C to 15°C. The maximal blocking temperature below which the axon could be blocked was increased from 22°C to 37°C
as the stimulation frequency was increased from 4 to 8 kHz. The maximal blocking temperature was not influenced by axon diameter.
Simulation analysis also revealed that activation of potassium channels might determine the temperature–frequency relationship.
This study indicates that temperature might be one of the factors that cause the frequency discrepancy as reported in previous
animal studies.
Action Editor: Alain Destexhe 相似文献
105.
Rakesh Gopinathannair Brian Olshansky 《Indian pacing and electrophysiology journal》2009,9(6):334-341
Simple and cost-effective tools that identify patients at increased risk for adverse cardiovascular events are actively sought. High resting sinus heart rate and first degree AV block are easily recognized and commonly encountered findings in a cardiology practice. A growing body of epidemiological and clinical evidence has been shown them to be independent predictors of all-cause and cardiovascular mortality, both in the general population and in patients with structural heart disease. This paper reviews the important role of heart rate and first degree AV block in predicting cardiovascular outcomes, examines the pathophysiological mechanisms underlying this increased risk, and discusses the effectiveness of available therapies to favorably modify these risk factors. 相似文献
106.
MENG Yan ZHAO ChunYan ZHANG XueXin ZHAO HuaShan GUO LiRong Lü Bin ZHAO XueJian& YANG BaoXue Department of Pathophysiology School of Basic Medicine Jilin University Changchun China Department of Physiology Department of Medicine University of California San Francisco CA USA 《中国科学:生命科学英文版》2009,52(5):474-478
107.
RuiJie Zhang Xia Li YongShuai Jiang GuiYou Liu ChuanXing Li Fan Zhang Yun Xiao BinSheng Gong 《中国科学:生命科学英文版》2009,52(2):163-172
High-throughout single nucleotide polymorphism detection technology and the existing knowledge provide strong support for
mining the disease-related haplotypes and genes. In this study, first, we apply four kinds of haplotype identification methods
(Confidence Intervals, Four Gamete Tests, Solid Spine of LD and fusing method of haplotype block) into high-throughout SNP
genotype data to identify blocks, then use cluster analysis to verify the effectiveness of the four methods, and select the
alcoholism-related SNP haplotypes through risk analysis. Second, we establish a mapping from haplotypes to alcoholism-related
genes. Third, we inquire NCBI SNP and gene databases to locate the blocks and identify the candidate genes. In the end, we
make gene function annotation by KEGG, Biocarta, and GO database. We find 159 haplotype blocks, which relate to the alcoholism
most possibly on chromosome 1∼22, including 227 haplotypes, of which 102 SNP haplotypes may increase the risk of alcoholism.
We get 121 alcoholism-related genes and verify their reliability by the functional annotation of biology. In a word, we not
only can handle the SNP data easily, but also can locate the disease-related genes precisely by combining our novel strategies
of mining alcoholism-related haplotypes and genes with existing knowledge framework.
Supported by the National Natural Science Foundation of China (Grant Nos. 30570424, 60601010 and 30600367), the National High-Tech
Research and Development Program of China, (Grant No.2007AA02Z329), the Key Science and Technology Program of Heilongjiang
Province(Grant No.GB03C602-4), Natural Science Foundation of Heilongjiang Province (Grant No. F2008-02), Youth Science Foundation
of Harbin Medical University (Grant No. 060045) and Science Foundation of Heilongjiang Province Education Department (Grant
Nos. 11531113 and 1152hq28). 相似文献
108.
State environmental regulatory agencies in the U.S. often establish a default background standard for naturally occurring elements in the soil, water, and air. The background standard is determined and then used as a benchmark across the entire jurisdiction. A variety of statistical techniques are used to determine this standard, but often ignore any inherent spatial dependencies within the jurisdiction. If the analysis indicates a specific site exceeds the default standard, additional background sampling and analysis must usually be performed. Frequently, this additional sampling is found to be unnecessary simply because the natural background levels were elevated for this particular site. Conversely, potential contamination may be overlooked in areas where the natural background levels are much lower. Thus, a single default background standard seems inadequate within this context.
This paper proposes the use of dissimilarity coefficients based on kriging estimates as a means to regionalize background standards. Along with cluster analysis techniques, these dissimilarity coefficients provide a means to stratify the population into geographic sub-areas. A regulatory agency may now define multiple default background standards based on geographic location. To illustrate, this paper examines a case study concerning residential soil arsenic for 83 Michigan counties. 相似文献
109.
Kubrycht J Sigler K Růzicka M Soucek P Borecký J Jezek P 《Journal of molecular evolution》2006,63(5):691-706
Many structures and molecules closely related to those involved in the specific process of immunoglobulin (Ig) hypermutation existed before the appearance of primordial Ig genes. Consequently, these structures can be found even in animals and organisms distinct from vertebrates; likewise, homologues of hypermutation enzymes are present in a broad range of species, from bacteria to mammals. Our analysis, based predominantly on primary structure, demonstrates the existence of molecules similar to Ig domains, variable Ig domains (IGv), and antigen receptors (AR) in unicellular organisms, nonvertebrate metazoans, and nonvertebrate Coelomata, respectively. In addition, we deal here with some important structural properties of CDR1-like segments of the selected sponge adhesion molecule GCSAMS exhibiting chimerical Ig domain similarities, and demonstrate the occurrence of conserved regions corresponding to Ohno's modern intact primordial building block in the C-terminal part of IGv-related segments of nonvertebrate origin. The results of our analysis are also discussed with respect to the possible phylogeny of molecules preceding the hypothetical common antigen receptor ancestor. 相似文献
110.
Ginkgolides are potent blockers of the glycine receptor Cl- channel (GlyR) pore. We sought to identify their binding sites by comparing the effects of ginkgolides A, B and C and bilobalide on alpha1, alpha2, alpha1beta and alpha2beta GlyRs. Bilobalide sensitivity was drastically reduced by incorporation of the beta subunit. In contrast, the sensitivities to ginkgolides B and C were enhanced by beta subunit expression. However, ginkgolide A sensitivity was increased in the alpha2beta GlyR relative to the alpha2 GlyR but not in the alpha1beta GlyR relative to the alpha1 GlyR. We hypothesised that the subunit-specific differences were mediated by residue differences at the second transmembrane domain 2' and 6' pore-lining positions. The increased ginkgolide A sensitivity of the alpha2beta GlyR was transferred to the alpha1beta GlyR by the G2'A (alpha1 to alpha2 subunit) substitution. In addition, the alpha1 subunit T6'F mutation abolished inhibition by all ginkgolides. As the ginkgolides share closely related structures, their molecular interactions with pore-lining residues were amenable to mutant cycle analysis. This identified an interaction between the variable R2 position of the ginkgolides and the 2' residues of both alpha1 and beta subunits. These findings provide strong evidence for ginkgolides binding at the 2' pore-lining position. 相似文献