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171.
The general assumption among researchers on hemoglobin is that the intramolecular central cavity cross-bridging of Hb does not result in any generalized perturbations at the protein surface. A corollary of this is that central cavity cross-bridges are unlikely to influence the polymerization of deoxy HbS, since polymerization is a protein surface phenomenon involving the participation of multiple protein surface amino acid residues. In an attempt to evaluate this experimentally, we have introduced two low-O2-affinity-inducing central cavity cross-bridges into HbS, -sebacyl [between the two Lys-82() residues] and -fumaryl [between the two Lys-99() residues], and investigated their influence on the polymerization of the deoxy protein. The O2 affinities of the cross-bridged HbS exhibited sensitivity toward the buffer ions and pH in a cross-link-specific fashion. The modulation of the O2 affinity of these cross-bridged HbS in the presence of allosteric effectors, DPG and L-35, is also very distinct, reflecting the differences in the conformational features these two cross-bridges induce within the central cavity at the respective effector-binding domains. In addition, the -fumaryl cross bridge inhibited the polymerization, reflecting the perturbation of the microenvironment of one or more intermolecular contact residues, protein surface residues, as a consequence of the central cavity cross-bridge. On the other hand, the -sebacyl cross-bridge exerted a slight potentiating effect on the polymerization of HbS. This reflects the fact that the perturbations at the protein surface are limited and favor polymerization. The results presented demonstrate that the structural changes induced by the central cavity cross-bridges are very specific and not simply restricted to the sites of modification, but are propagated to distant sites/domains, both within and outside the central cavity. It is conceivable that other surface regions that are not involved in the polymerization could also experience similar structural/conformational consequences. These results should be taken into consideration in designing intramolecularly cross-bridged asymmetric hybrid HbS for mapping the contribution of the intermolecular contact residues in the cis and trans dimers of deoxy HbS during polymerization. 相似文献
172.
Schauble S King CC Darshi M Koller A Shah K Taylor SS 《The Journal of biological chemistry》2007,282(20):14952-14959
Due to the numerous kinases in the cell, many with overlapping substrates, it is difficult to find novel substrates for a specific kinase. To identify novel substrates of cAMP-dependent protein kinase (PKA), the PKA catalytic subunit was engineered to accept bulky N(6)-substituted ATP analogs, using a chemical genetics approach initially pioneered with v-Src (1). Methionine 120 was mutated to glycine in the ATP-binding pocket of the catalytic subunit. To express the stable mutant C-subunit in Escherichia coli required co-expression with PDK1. This mutant protein was active and fully phosphorylated on Thr(197) and Ser(338). Based on its kinetic properties, the engineered C-subunit preferred N(6)(benzyl)-ATP and N(6)(phenethyl)-ATP over other ATP analogs, but still retained a 30 microm K(m) for ATP. This mutant recombinant C-subunit was used to identify three novel PKA substrates. One protein, a novel mitochondrial ChChd protein, ChChd3, was identified, suggesting that PKA may regulate mitochondria proteins. 相似文献
173.
Sathish Kumar Paramashivam Kalaivani Elayaperumal Boopala bhagavan Natarajan Manjula devi Ramamoorthy Suganthana Balasubramanian Kannan Narayanan Dhiraviam 《Bioinformation》2015,11(2):73-84
Angiogenesis is the formation of new blood vessels from preexisting vascular network that plays an important role in the tumor
growth, invasion and metastasis. Anti-angiogenesis targeting tyrosine kinases such as vascular endothelial growth factor receptor 2
(VEGFR2) and platelet derived growth factor receptor β (PDGFRβ) constitutes a successful target for the treatment of cancer. In this
work, molecular docking studies of three bioflavanoid such as indigocarpan, mucronulatol, indigocarpan diacetate and two
diterpenes namely erythroxydiol X and Y derived from Indigofera aspalathoides as PDGFRβ and VEGFR2 inhibitors were performed
using computational tools. The crystal structures of two target proteins were retrieved from PDB website. Among the five
compounds investigated, indigocarpan exhibited potent binding energy ΔG = -7.04 kcal/mol with VEGFR2 and ΔG = -4.82 with
PDGFRβ compared to commercially available anti-angiogenic drug sorafenib (positive control). Our results strongly suggested that
indigocarpan is a potent angiogenesis inhibitor as ascertained by its potential interaction with VEGFR2 and PDGFRβ. This
hypothesis provides a better insight to control metastasis by blocking angiogenesis. 相似文献
174.
In mammalian fertilization, paternal chromatin is exhaustively remodeled, yet the maternal contribution to this process is unknown. To address this, we prevented the induction of meiotic exit by spermatozoa and examined sperm chromatin remodeling in metaphase II (mII) oocytes. Methylation of paternal H3-K4 and H3-K9 remained low, unlike maternal H3, although paternal H3-K4 methylation increased in zygotes. Thus, mII cytoplasm can sustain epigenetic asymmetry in a cell-cycle dependent manner. Paternal genomic DNA underwent oocyte-mediated cytosine demethylation and acquired maternally-derived K12-acetylated H4 (AcH4-K12) independently of microtubule assembly and maternal chromatin. AcH4-K12 persisted without typical maturation-associated deacetylation, irrespective of paternal pan-genomic cytosine methylation. Contrastingly, somatic cell nuclei underwent rapid H4 deacetylation; sperm and somatic chromatin exhibited asymmetric AcH4-K12 dynamics simultaneously within the same mII oocyte. Inhibition of somatic histone deacetylation revealed endogenous histone acetyl transferase activity. Oocytes thus specify the histone acetylation status of given nuclei by differentially targeting histone deacetylase and acetyl transferase activities. Asymmetric H4 acetylation during and immediately after fertilization was dispensable for development when both parental chromatin sets were hyperacetylated. These studies delineate non-zygotic chromatin remodeling and suggest a powerful model with which to study de novo genomic reprogramming. 相似文献
175.
176.
S. Raghothama Manjula Chaddha S. Banumathi Krishnan Ravikumar D. Velmurugan P. Balaram 《Biopolymers》1998,45(3):191-202
The crystal structure of the model tripeptide Boc-Aib-Gly-Leu-OMe ( 1 ) reveals two independent molecules in the asymmetric unit that adopt “enantiomeric” type I and type I′ β-turn conformations with the Aib and Gly residues occupying the corner (i + 1 and i + 2) positions. 13C cross polarization and magic angle sample spinning spectra in the solid state also support the coexistence of two conformational species. 13C-nmr in CDCl3 establishes the presence of a single species or rapid exchange between conformations. 400 MHz 1H-nmr provides evidence for conformational exchange involving a major and minor species, with β-turn conformations supported by the low solvent exposure of Leu(3) NH and the observation of NiH ↔ Ni+1H nuclear Overhauser effects. CD bands in the region 190–230 nm are positive, supporting a major population of type I′ β-turns. The isomeric peptide, Boc-Gly-Leu-Aib-OMe ( 2 ), adopts an “open” type II′ β-turn conformation in crystals. Solid state and solution nmr support population of a single conformational species. Chiral perturbation introduced outside the folded region of peptides may provide a means of modulating screw sense in achiral sequences. © 1998 John Wiley & Sons, Inc. Biopoly 45: 191–202, 1998 相似文献
177.
The naturally occurring mutants of DDB are impaired in stimulating nuclear import of the p125 subunit and E2F1-activated transcription.
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In the present study, we report the cloning and sequence characterization of two isoforms of osmotin, an antifungal PR-5 gene homologue, from a salicylic acid-induced subtracted cDNA library earlier generated in Piper colubrinum. The larger form of the gene is 693 bp long, encoding a 21.5 kDa protein. The smaller form comprises a 543 bp long coding
sequence which code for a protein of 16.4 kDa. A notable feature of the smaller form was a prominent internal deletion of
150 bp besides certain point mutations. Cloned isoforms of osmotin from resistant species could be candidates for molecular
breeding for the improvement of black pepper as well as candidates for the study of structure based mechanism of antifungal
activity attributed to PR-5 family. 相似文献