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921.
Li H Asberom T Bara TA Clader JW Greenlee WJ Josien HB McBriar MD Nomeir A Pissarnitski DA Rajagopalan M Xu R Zhao Z Song L Zhang L 《Bioorganic & medicinal chemistry letters》2007,17(22):6290-6294
Development of cis-2,4,6-trisubstituted piperidine N-arylsulfonamides as gamma-secretase inhibitors for the potential treatment of Alzheimer's disease (AD) is reported. 相似文献
922.
Xu M Shashilov VA Ermolenkov VV Fredriksen L Zagorevski D Lednev IK 《Protein science : a publication of the Protein Society》2007,16(5):815-832
Amyloid fibril depositions are associated with many neurodegenerative diseases as well as amyloidosis. The detailed molecular mechanism of fibrillation is still far from complete understanding. In our previous study of in vitro fibrillation of hen egg white lysozyme, an irreversible partially unfolded intermediate was characterized. A similarity of unfolding kinetics found for the secondary and tertiary structure of lysozyme using deep UV resonance Raman (DUVRR) and tryptophan fluorescence spectroscopy leads to a hypothesis that the unfolding might be a two-state transition. In this study, chemometric analysis, including abstract factor analysis (AFA), target factor analysis (TFA), evolving factor analysis (EFA), multivariate curve resolution-alternating least squares (ALS), and genetic algorithm, was employed to verify that only two principal components contribute to the DUVRR and fluorescence spectra of soluble fraction of lysozyme during the fibrillation process. However, a definite conclusion on the number of conformers cannot be made based solely on the above spectroscopic data although chemometric analysis suggested the existence of two principal components. Therefore, electrospray ionization mass spectrometry (ESI-MS) was also utilized to address the hypothesis. The protein ion charge state distribution (CSD) envelopes of the incubated lysozyme were well fitted with two principal components. Based on the above analysis, the partial unfolding of lysozyme during in vitro fibrillation was characterized quantitatively and proven to be a two-state transition. The combination of ESI-MS and Raman and fluorescence spectroscopies with advanced statistical analysis was demonstrated to be a powerful methodology for studying protein structural transformations. 相似文献
923.
Frenkiel-Krispin D Wolf SG Albeck S Unger T Peleg Y Jacobovitch J Michael Y Daube S Sharon M Robinson CV Svergun DI Fass D Tzfira T Elbaum M 《The Journal of biological chemistry》2007,282(6):3458-3464
Agrobacterium tumefaciens infects plant cells by the transfer of DNA. A key factor in this process is the bacterial virulence protein VirE2, which associates stoichiometrically with the transported single-stranded (ss) DNA molecule (T-strand). As observed in vitro by transmission electron microscopy, VirE2-ssDNA readily forms an extended helical complex with a structure well suited to the tasks of DNA protection and nuclear import. Here we have elucidated the role of the specific molecular chaperone VirE1 in regulating VireE2-VirE2 and VirE2-ssDNA interactions. VirE2 alone formed functional filamentous aggregates capable of ssDNA binding. In contrast, co-expression with VirE1 yielded monodisperse VirE1-VirE2 complexes. Cooperative binding of VirE2 to ssDNA released VirE1, resulting in a controlled formation mechanism for the helical complex that is further promoted by macromolecular crowding. Based on this in vitro evidence, we suggest that the constrained volume of the VirB channel provides a natural site for the exchange of VirE2 binding from VirE1 to the T-strand. 相似文献
924.
Solution structure of selenoprotein W and NMR analysis of its interaction with 14-3-3 proteins 总被引:1,自引:0,他引:1
Aachmann FL Fomenko DE Soragni A Gladyshev VN Dikiy A 《The Journal of biological chemistry》2007,282(51):37036-37044
Selenium is a trace element with significant biomedical potential. It is essential in mammals due to its occurrence in several proteins in the form of selenocysteine (Sec). One of the most abundant mammalian Sec-containing proteins is selenoprotein W (SelW). This protein of unknown function has a broad expression pattern and contains a candidate CXXU (where U represents Sec) redox motif. Here, we report the solution structure of the Sec13-->Cys variant of mouse SelW determined through high resolution NMR spectroscopy. The protein has a thioredoxin-like fold with the CXXU motif located in an exposed loop similarly to the redox-active site in thioredoxin. Protein dynamics studies revealed the rigidity of the protein backbone and mobility of two external loops and suggested a role of these loops in interaction with SelW partners. Molecular modeling of structures of other members of the Rdx family based on the SelW structure identified new conserved features in these proteins, including an aromatic cluster and interacting loops. Our previous study suggested an interaction between SelW and 14-3-3 proteins. In the present work, with the aid of NMR spectroscopy, we demonstrated specificity of this interaction and identified mobile loops in SelW as interacting surfaces. This finding suggests that 14-3-3 are redox-regulated proteins. 相似文献
925.
King-Scott J Nowak E Mylonas E Panjikar S Roessle M Svergun DI Tucker PA 《The Journal of biological chemistry》2007,282(52):37717-37729
The full-length, two-domain response regulator RegX3 from Mycobacterium tuberculosis is a dimer stabilized by three-dimensional domain swapping. Dimerization is known to occur in the OmpR/PhoB subfamily of response regulators upon activation but has previously only been structurally characterized for isolated receiver domains. The RegX3 dimer has a bipartite intermolecular interface, which buries 2357 A(2) per monomer. The two parts of the interface are between the two receiver domains (dimerization interface) and between a composite receiver domain and the effector domain of the second molecule (interdomain interface). The structure provides support for the importance of threonine and tyrosine residues in the signal transduction mechanism. These residues occur in an active-like conformation stabilized by lanthanum ions. In solution, RegX3 exists as both a monomer and a dimer in a concentration-dependent equilibrium. The dimer in solution differs from the active form observed in the crystal, resembling instead the model of the inactive full-length response regulator PhoB. 相似文献
926.
927.
CAN—a pan-carnivore SINE family 总被引:2,自引:0,他引:2
Short retroposons or short interspersed elements (SINEs) constituting 5–10% genome have been isolated from various organisms.
CAN SINEs initially found in American mink were named after dogs (Canis), and the range of their distribution in the genomes
of carnivores and mammals in general remained topical. Here we demonstrate CAN sequences in representatives of all carnivore
families, but not beyond carnivores, on the basis of sequence bank search and genomic PCR. Analysis of their distribution
supports division of carnivores into caniform (dogs, mustelids, raccoons, bears, and pinnipeds) and feliform (cats, civets,
and hyenas) lineages. CAN structure is considered in the context of their function and evolution.
Received: 13 July 2001 / Accepted: 18 September 2001 相似文献
928.
Eddy Low Satheesh Nair Timothy Shiau Barbara Belisle Dmitri Debabov Chris Celeri Meghan Zuck Ron Najafi Nafsika Georgopapadakou Rakesh Jain 《Bioorganic & medicinal chemistry letters》2009,19(1):196-198
2-Dichloroamino-2-methyl-propane-1-sulfonic acid sodium salt (2a), a stable derivative of endogenous N,N-dichlorotaurine (1), has been identified and is under development as a topical antimicrobial agent. Structure–activity relationships of analogs were explored to achieve optimal antimicrobial activity with minimal mammalian toxicity while maintaining the desired stability. All the analogs synthesized showed antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans in the range of 1–128 μg/mL and cytotoxicity against mammalian L929 cells in the range 80–1900 μg/mL. 相似文献
929.
Two types of silanes, namely aklylalkoxysilanes and arylalkoxysilanes, were used for wood impregnation aiming at hydrophobisation of the ligno-cellulose material. The suggested mixture of alkyltriethoxysilanes and dialkyldiethoxysilanes improved water repellence when compared to conventionally used silanes. An attempt to immobilise boric acid with the siloxane matrix was also done. Decay resistance of the treated samples was tested by soil-jar test using the brown rot fungus Postia placenta.Features of the impregnated wood such as moisture content, swelling, anti-swelling efficacy and weight percentage gain were not significantly related to the mass loss of samples caused by the fungus. Samples impregnated with EtPhSi(OEt)2 silanes showed improved durability (3.5–11.5% mass loss). Addition of boric acid to two of the silanols showed the best result for durability of wood, i.e. the lowest mass loss of 2.3 and 1.1%. These treatments upgraded the wood to “very durable”, a significant improvement from its natural status, i.e. slightly durable. The studied alkoxysilanes have moderate ability to penetrate the wood cell wall and hence to improve its hydrophobicity. These silanes are promising although more research should be carried out on the degree of oligomer polymerisation in the wood cell wall. 相似文献
930.