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951.
Röhrich A Bergmann R Kretzschmann A Noll S Steinbach J Pietzsch J Stephan H 《Journal of inorganic biochemistry》2011,105(6):821-832
New macrocyclic 1,4,8,11-tetraazacyclotetradecane (cyclam) derivatives with 1, 2 and 4 neurotensin(8-13) units 4, 5 and 7 have been synthesized. Compounds 4 and 5 were prepared by the reaction of non-stabilized neurotensin(8-13) and cyclamtetrapropionic acid 2 using 1-ethyl-3-(3-dimethylaminocarbonyl)carbodiimide-hydrochloride and N-hydroxysulfosuccinimide. The tetrameric compound 7 was synthesized by Michael addition of neurotensin(8-13) acrylamide 6 and cyclam 1. The copper(II) complexation behavior of 4, 5 and 7 was investigated by UV/visible spectrophotometry and shows that the metal center resides inside the N4 chromophore with additional apical interactions established with pendant arms. The novel tetrabranched NT(8-13) cyclam 7 with nanomolar neurotensin receptor 1 binding affinity was efficiently radiolabeled with 64Cu under mild conditions. 64Cu ⊂ 7 showed slow transchelation in the presence of a large amount of cyclam as competing ligand, while it completely remains intact in the presence of EDTA. The in vivo behavior of 64Cu ⊂ 7 was studied in rats and mice. The metabolic stability in rodent models was high with a half-life of intact 64Cu ⊂ 7 in plasma of 34 min in rats and 60 min in the mice, respectively. The binding affinity was high enough to demonstrate in vivo binding of 64Cu ⊂ 7 to NTR1 overexpressing HT-29 tumor xenotransplants in nude mice. Regarding elimination, 64Cu ⊂ 7 showed a substantial renal and reticuloendothelial accumulation. On the other hand, metabolization of the compound in vivo with a resulting metabolite—postulated to be the 64Cu-cyclam-tetraarginine complex—also showed long retention in the circulating blood, preventing a better contrast of tumor imaging. 相似文献
952.
Guengerich FP 《The Journal of biological chemistry》2011,286(29):25417
Mass spectrometry is a powerful technique with many applications in biology as well as chemistry and physics. The increases in sensitivity and resolution of the instruments, coupled with improvements in the analysis of data, have opened new dimensions in analyses of complex biological systems. Examples presented here include drug metabolism, lipid analysis, metabolomics, quantitative proteomics, direct analysis of intact proteins, and imaging of both small molecules and proteins in tissues. 相似文献
953.
Pingali SV O'Neill HM McGaughey J Urban VS Rempe CS Petridis L Smith JC Evans BR Heller WT 《The Journal of biological chemistry》2011,286(37):32801-32809
Cellobiohydrolase I (Cel7A) of the fungus Trichoderma reesei (now classified as an anamorph of Hypocrea jecorina) hydrolyzes crystalline cellulose to soluble sugars, making it of key interest for producing fermentable sugars from biomass for biofuel production. The activity of the enzyme is pH-dependent, with its highest activity occurring at pH 4-5. To probe the response of the solution structure of Cel7A to changes in pH, we measured small angle neutron scattering of it in a series of solutions having pH values of 7.0, 6.0, 5.3, and 4.2. As the pH decreases from 7.0 to 5.3, the enzyme structure remains well defined, possessing a spatial differentiation between the cellulose binding domain and the catalytic core that only changes subtly. At pH 4.2, the solution conformation of the enzyme changes to a structure that is intermediate between a properly folded enzyme and a denatured, unfolded state, yet the secondary structure of the enzyme is essentially unaltered. The results indicate that at the pH of optimal activity, the catalytic core of the enzyme adopts a structure in which the compact packing typical of a fully folded polypeptide chain is disrupted and suggest that the increased range of structures afforded by this disordered state plays an important role in the increased activity of Cel7A through conformational selection. 相似文献
954.
Wellhauser L Luna-Chavez C D'Antonio C Tainer J Bear CE 《The Journal of biological chemistry》2011,286(8):6733-6741
ATP binding enhances the activity of ClC-5, the transporter mutated in Dent disease, a disease affecting the renal proximal tubule. Previously, the ATP binding site was revealed in x-ray crystal structures of the cytoplasmic region of this membrane protein. Disruption of this site by mutagenesis (Y617A-ClC-5) reduced the functional expression and ATP-dependent regulation of the full-length transporter in Xenopus oocytes. However, insight into the conformational changes underlying ATP-dependent regulation is lacking. Here, we show that ATP binding induces a change in protein conformation. Specifically, small angle x-ray scattering experiments indicate that ATP binding promotes a clamp-like closure of the isolated ClC-5 carboxyl-terminal region. Limited proteolysis studies show that ATP binding induces conformational compaction of the carboxyl-terminal region in the intact membrane protein as well. In the context of fibroblasts and proximal tubule epithelial cells, disruption of the ATP binding site in full-length ClC-5 (Y617A-ClC-5) led to a defect in processing and trafficking out of the endoplasmic reticulum. These latter findings account for the decrease in functional expression previously reported for this ATP-binding mutant and prompt future study of a model whereby conformational compaction caused by ATP binding promotes biosynthetic maturation. 相似文献
955.
Compton EL Karinou E Naismith JH Gabel F Javelle A 《The Journal of biological chemistry》2011,286(30):27058-27067
The SLC26/SulP (solute carrier/sulfate transporter) proteins are a superfamily of anion transporters conserved from bacteria to man, of which four have been identified in human diseases. Proteins within the SLC26/SulP family exhibit a wide variety of functions, transporting anions from halides to carboxylic acids. The proteins comprise a transmembrane domain containing between 10-12 transmembrane helices followed a by C-terminal cytoplasmic sulfate transporter and anti-sigma factor antagonist (STAS) domain. These proteins are expected to undergo conformational changes during the transport cycle; however, structural information for this family remains sparse, particularly for the full-length proteins. To address this issue, we conducted an expression and detergent screen on bacterial Slc26 proteins. The screen identified a Yersinia enterocolitica Slc26A protein as the ideal candidate for further structural studies as it can be purified to homogeneity. Partial proteolysis, co-purification, and analytical size exclusion chromatography demonstrate that the protein purifies as stable oligomers. Using small angle neutron scattering combined with contrast variation, we have determined the first low resolution structure of a bacterial Slc26 protein without spectral contribution from the detergent. The structure confirms that the protein forms a dimer stabilized via its transmembrane core; the cytoplasmic STAS domain projects away from the transmembrane domain and is not involved in dimerization. Supported by additional biochemical data, the structure suggests that large movements of the STAS domain underlie the conformational changes that occur during transport. 相似文献
956.
957.
Plant microRNAs (miRNAs) are single-stranded 20-22 nt small RNAs (sRNA) that are produced from their own genes. We have developed a de novo genome-wide approach for the computational identification of novel plant miRNAs based on the integration of the complete genome sequence with sRNA libraries. It comprises three modules - the clustering module identifies genomic regions that have two closely-located unidirectional sRNA clusters, the mirplan module explores the secondary structure of the genomic regions, and the duplex module predicts miRNA/miRNA* duplexes. We applied our approach to the Brachypodium genome and publicly available sRNA libraries and predicted 102 miRNAs. Our results extend the list of known miRNAs with 58 novel miRNAs and define the genomic loci of all predicted miRNAs. Because this approach considers specific features of plant miRNAs, it can be employed for the analysis of the genome and sRNA libraries generated for plant species to achieve systematic miRNA discovery. 相似文献
958.
Chang DJ Jeong MY Song J Jin CY Suh YG Kim HJ Min KH 《Bioorganic & medicinal chemistry letters》2011,21(23):7050-7053
1,3,4-Oxadiazole derivatives were found to enhance astrocyte differentiation in rat fetal neural stem cells (NSCs). Differentiation activity was assessed by immunocytochemistry and analysis of mRNA expression of astrocyte markers, GFAP and S100. Compounds 7 and 8 showed approximately a two-fold increase in astrocyte differentiation without engagement of neuronal differentiation and detectable cytotoxicity. 相似文献
959.
Khaing Z Kang D Camelio AM Schmidt CE Siegel D 《Bioorganic & medicinal chemistry letters》2011,21(16):4808-4812
The use of small molecule surrogates of growth factors that directly or indirectly promote growth represents an attractive approach to regenerative medicine. With synthetic access to clovanemagnolol, a small molecule initially isolated from the bark of the Bigleaf Magnolia tree, we have examined the small molecule’s ability to promote growth of embryonic hippocampal and cortical neurons in serum-free medium. Comparisons with magnolol, a known promoter of growth, reveals that clovanmagnolol is a potent neurotrophic agent, promoting neuronal growth at concentrations of 10 nM. In addition, both clovanemagnolol and magnolol promote growth through a biphasic dose response. 相似文献
960.
Roland K.EBERWEIN 《云南植物研究》2011,33(1):75-79
The continuously increasing demands on botanic gardens during the last few decades have led to a huge in increase administration and an urgent need for additional specialized personnel, especially botanists, teachers, database specialists and administrative staff. Instead of meeting these requirements, many botanic gardens are faceing a severe decrease in funding and personnel. Larger gardens provide the opportunity to distribute several tasks to different employees, whereas small gardens are short staffed and often nn by a single curator who has to fulfill all functions. In order to meet actual demands more easily, the Austrian botanic gardens are linked nationally via an active workgroup.This network not only allows the distribution of information but also facilitates the sharing of duties. A listserver speeds up the communication and correspondence within the workgroup, collection priorities and projects (e. g., GSPC) are coordinated, seedbanking becomes decentralized, printedmatters are shared and distributed, etc. Small gardens with only few employees can participate in projects by taking on small-ideally using with their special resources-in order not to fall behind. In addition, there is also an urgent need for international networking by means of plant and seed exchange (Index Semihum), BGCI membership, discussion groups, personal contacts and projects. Mission statements,special marketing strategies for public relations, integrating projects of other workgroup members and adapted public awareness programs are important to focus attention to small gardens and to help them keep alive. 相似文献