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121.
Copper(II)-zinc(II) bimetallic imidazolate metal-organic framework compounds of composition CuaZnbIm2(a + b) (Im = C3H3N2), including Cu2ZnIm6 (1), were prepared in high yields from the metal oxides under mild aqueous conditions using a novel acid catalysis method. Mild acidic hydrothermal treatment of paramagnetic 1 (≥120 °C) gave diamagnetic Cu(I)-containing Cu2ZnIm4 (2) in high yield. The formation mechanism of 2 involves electron transfer from Im− to Cu(II), with concomitant formation of the unusual cyclotriimidazole, C9H6N6. Air-stable 2, characterized by single-crystal X-ray diffraction, crystallized in the tetragonal space group , with a = b = 10.9623(3), c = 6.3231(4) Å, α = β = γ = 90°, V = 759.86(6) Å3, and Z = 1. 相似文献
122.
123.
Tyler J. Glembo 《Biophysical journal》2010,98(6):1046-1054
Although proteins are a fundamental unit in biology, the mechanism by which proteins fold into their native state is not well understood. In this work, we explore the assembly of secondary structure units via geometric constraint-based simulations and the effect of refinement of assembled structures using reservoir replica exchange molecular dynamics. Our approach uses two crucial features of these methods: i), geometric simulations speed up the search for nativelike topologies as there are no energy barriers to overcome; and ii), molecular dynamics identifies the low free energy structures and further refines these structures toward the actual native conformation. We use eight α-, β-, and α/β-proteins to test our method. The geometric simulations of our test set result in an average RMSD from native of 3.7 Å and this further reduces to 2.7 Å after refinement. We also explore the question of robustness of assembly for inaccurate (shifted and shortened) secondary structure. We find that the RMSD from native is highly dependent on the accuracy of secondary structure input, and even slightly shifting the location of secondary structure along the amino acid sequence can lead to a rapid decrease in RMSD to native due to incorrect packing. 相似文献
124.
B.J. Fennell A. Darmanin-Sheehan V. Calabro L. Wu W. Cao O. Cunningham 《Journal of molecular biology》2010,400(2):155-333
The shark antigen-binding VNAR domain has the potential to provide an attractive alternative to traditional biotherapeutics based on its small size, advantageous physiochemical properties, and unusual ability to target clefts in enzymes or cell surface molecules. The VNAR shares many of the properties of the well-characterised single-domain camelid VHH but is much less understood at the molecular level. We chose the hen-egg-lysozyme-specific archetypal Type I VNAR 5A7 and used ribosome display in combination with error-prone mutagenesis to interrogate the entire sequence space. We found a high level of mutational plasticity across the VNAR domain, particularly within the framework 2 and hypervariable region 2 regions. A number of residues important for affinity were identified, and a triple mutant combining A1D, S61R, and G62R resulted in a KD of 460 pM for hen egg lysozyme, a 20-fold improvement over wild-type 5A7, and the highest KD yet reported for VNAR-antigen interactions. These findings were rationalised using structural modelling and indicate the importance of residues outside the classical complementarity determining regions in making novel antigen contacts that modulate affinity. We also located two solvent-exposed residues (G15 and G42), distant from the VNAR paratope, which retain function upon mutation to cysteine and have the potential to be exploited as sites for targeted covalent modification. Our findings with 5A7 were extended to all known NAR structures using an in-depth bioinformatic analysis of sequence data available in the literature and a newly generated VNAR database. This study allowed us to identify, for the first time, both VNAR-specific and VNAR/Ig VL/TCR Vα overlapping hallmark residues, which are critical for the structural and functional integrity of the single domain. Intriguingly, each of our designated VNAR-specific hallmarks align precisely with previously defined mutational ‘cold spots’ in natural nurse shark cDNA sequences. These findings will aid future VNAR engineering and optimisation studies towards the development of VNAR single-domain proteins as viable biotherapeutics. 相似文献
125.
Alejandra Hernández-Santoyo Luis del Pozo Yauner Deyanira Fuentes-Silva Enrique Rudiño-Piñera Eduardo Horjales Adela Rodríguez-Romero 《Journal of molecular biology》2010,396(2):280-292
Systemic amyloid light-chain (LC) amyloidosis is a disease process characterized by the pathological deposition of monoclonal LCs in tissue. All LC subtypes are capable of fibril formation although λ chains, particularly those belonging to the λ6 type, are overrepresented. Here, we report the thermodynamic and in vitro fibrillogenic properties of several mutants of the λ6 protein 6aJL2 in which Pro7 and/or His8 was substituted by Ser or Pro. The H8P and H8S mutants were almost as stable as the wild-type protein and were poorly fibrillogenic. In contrast, the P7S mutation decreased the thermodynamic stability of 6aJL2 and greatly enhanced its capacity to form amyloid-like fibrils in vitro. The crystal structure of the P7S mutant showed that the substitution induced both local and long-distance effects, such as the rearrangement of the VL (variable region of the light chain)-VL interface. This mutant crystallized in two orthorhombic polymorphs, P212121 and C2221. In the latter, a monomer that was not arranged in the typical Bence-Jones dimer was observed for the first time. Crystal-packing analysis of the C2221 lattice showed the establishment of intermolecular β-β interactions that involved the N-terminus and β-strand B and that these could be relevant in the mechanism of LC fibril formation. Our results strongly suggest that Pro7 is a key residue in the conformation of the N-terminal sheet switch motif and, through long-distance interactions, is also critically involved in the contacts that stabilized the VL interface in λ6 LCs. 相似文献
126.
GIS和遥感技术在生态安全评价与生物多样性保护中的应用 总被引:1,自引:0,他引:1
综合近年来国内外生态安全评价和生物多样性保护领域的研究成果:简要总结了地理信息系统(GIS)和遥感(RS)技术在生态学热点领域的应用研究现状和特点;归纳论述了GIS和RS在生态安全评价和生物多样性保护研究中存在的不足;在此基础上,尝试性地提出了可扩展的集成研究框架——"生产线"框架;最后探讨了GIS和RS技术与生态学集成研究的未来发展趋势。 相似文献
127.
The 2-D K(I)-tetrazole metal-organic complex, [K2(4-TPA)2(H2O)2]n (1), which is constructed by the [K2O4N]n inorganic skeleton chains bridged by the 4-TPA linkers, has been synthesized and characterized by single crystal X-ray crystallography and temperature-dependence dielectric constant(ε) measurement under the alternating electric field, (4-TPA = 2-(4-(1H-tetrazol-5-yl)pyridinium-1-yl) acetate). The ε of temperature dependence remains unchanged almost within the measured temperature range of 90 K to 430 K at 1 M Hz, and the ε of frequency dependence shows a significant decline from 6.7 to 4.6 within the measured frequency range of 200-1 MHz at room temperature. And it is consistent with the low dielectric loss (ε2/ε1) behavior, which is attributed to the highly ordered polarization mechanism. 相似文献
128.
Seungbong Han Adin‐Cristian Andrei Kam‐Wah Tsui 《Biometrical journal. Biometrische Zeitschrift》2010,52(2):222-232
When drawing large‐scale simultaneous inference, such as in genomics and imaging problems, multiplicity adjustments should be made, since, otherwise, one would be faced with an inflated type I error. Numerous methods are available to estimate the proportion of true null hypotheses π0, among a large number of hypotheses tested. Many methods implicitly assume that the π0 is large, that is, close to 1. However, in practice, mid‐range π0 values are frequently encountered and many of the widely used methods tend to produce highly variable or biased estimates of π0. As a remedy in such situations, we propose a hierarchical Bayesian model that produces an estimator of π0 that exhibits considerably less bias and is more stable. Simulation studies seem indicative of good method performance even when low‐to‐moderate correlation exists among test statistics. Method performance is assessed in simulated settings and its practical usefulness is illustrated in an application to a type II diabetes study. 相似文献
129.
A novel parental bla(TEM) gene (bla(TEM-1G)), encoding a TEM-1 beta-lactamase (pI of 5.4) produced by the uropathogenic Escherichia coli strain FMV194 was isolated from a dog. We report PCR-restriction fragment length polymorphism analysis and nucleotide sequencing of this gene. The bla(TEM-1G) sequence was identical to the bla(TEM-1C) gene framework in the coding and promoter (P3) regions, except for a silent G(604)-->T mutation in the coding region. Molecular phylogenetic analysis of parental bla(TEM) genes indicated two distinct groups, one comprising bla(TEM-1F) and bla(TEM-2). The other group comprises bla(TEM-1C) which is the probable ancestor of bla(TEM-1A), bla(TEM-1D) and bla(TEM-1G). The bla(TEM-1G) gene has the same framework as a gene encoding an inhibitor-resistant TEM beta-lactamase produced by an E. coli strain of human origin. Thus, parental bla(TEM) genes encoding beta-lactamases in E. coli strains isolated from different host species, in this case human and canine, may be phylogenetically very close. 相似文献
130.
Törjék O Berger D Meyer RC Müssig C Schmid KJ Rosleff Sörensen T Weisshaar B Mitchell-Olds T Altmann T 《The Plant journal : for cell and molecular biology》2003,36(1):122-140
The major goal of this project was the establishment of a tool for rapid mapping of new mutations and genotyping in Arabidopsis consisting of at least 100 evenly spaced framework markers. We assembled a single nucleotide polymorphism (SNP)-based marker set consisting of 112 polymorphic sites with average spacing of 1.15 Mbp derived from an SNP database that we recently developed. This information was used to set up efficient SNP detection reactions based on multiplexed primer extension assays. The 112 Columbia (Col-0)/C24 framework markers were used to assemble 18 multiplexed SNaPshot assays with which up to eight separate loci can be genotyped in a single-tube/single-capillary format. In addition, for 110 framework markers matrix-assisted laser desorption/ionization time of flight (MALDI-ToF) assays have been established for high throughput analyses. We demonstrated the usefulness and the robustness of both procedures of this tool by genotyping 48 BC3F1 individuals created between the accessions Col-0 and C24. Subsets of 10-62 of the established markers discriminate between various combinations of the accessions Col-0, C24, Landsberg erecta (Ler), Cape Verdi Islands (Cvi) and Niederzenz (Nd). Using a subset of 17 evenly distributed and established SNP markers that are also polymorphic between Ler and Col-0, we were able to rapidly map a mutant gene (tbr1) to an interval of 2.3 Mbp in an Ler (tbr1) x Col-0 cross. 相似文献