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31.
In the ribosome-independent biosynthesis of peptide natural products, amino acid building blocks are generally activated in the form of phosphoesters, esters, or thioesters prior to amide bond formation. Following the recent discovery of bacterial enzymes that utilize an aminoacyl ester with a transfer ribonucleic acid (tRNA) in primary metabolism, the number of tRNA-dependent enzymes used in biosynthetic studies of peptide natural products has increased steadily. In this review, we summarize the rapidly growing knowledge base regarding two types of tRNA-dependent enzymes, which are structurally and functionally distinct. Initially, we focus on enzymes with the GCN5-related N-acetyltransferase fold and discuss the catalytic function and aminoacyl-tRNA recognition. Next, newly found peptide-amino acyl tRNA ligases and their ATP-dependent reactions are highlighted. 相似文献
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Alexander S. Williams Scott Lovell Asokan Anbanandam Rahif El‐Chami James G. Bann 《Protein science : a publication of the Protein Society》2009,18(11):2277-2286
Domain 4 of the anthrax protective antigen (PA) plays a key role in cellular receptor recognition as well as in pH-dependent pore formation. We present here the 1.95 Å crystal structure of domain 4, which adopts a fold that is identical to that observed in the full-length protein. We have also investigated the structural properties of the isolated domain 4 as a function of pH, as well as the pH-dependence on binding to the von Willebrand factor A domain of capillary morphogenesis protein 2 (CMG2). Our results provide evidence that the isolated domain 4 maintains structure and interactions with CMG2 at pH 5, a pH that is known to cause release of the receptor on conversion of the heptameric prepore (PA63)7 to a membrane-spanning pore. Our results suggest that receptor release is not driven solely by a pH-induced unfolding of domain 4. 相似文献
36.
Thiébot Bénédicte Langris Monique Bonnamy Pierre-Jacques Bocquet Jean 《Molecular and cellular biochemistry》1998,187(1-2):99-112
The effects of an increase in intracellular cAMP concentration on proteoglycan (PG) synthesis by peritubular (PT) cells from immature rat testis were investigated. In the presence of dBcAMP for 72 h, the [3H]-hexosamine incorporation in secreted PG and in cellassociated PG was reduced, whereas [35S]-sulfate radioactivity was enhanced in secreted PG and not affected in cell-associated PG. Cholera toxin and IBMX, known to generate high intracellular cAMP levels, induced similar changes. Cyclic AMP did not alter PG protein moiety synthesis but enhanced PG turnover. Cholera toxin and dBcAMP profoundly modified PG characteristics: (1) Apparent molecular weight of PG was increased. (2) This was due to an increase in glycosaminoglycans (heparan sulfate (HS) and chondroitin sulfate (CS)) length. (3) The number of glycosaminoglycan chains was presumably reduced. (4) Heparan sulfate and chondroitin sulfate chains of medium and cell layer-associated PG appeared oversulfated. (5) The pattern of cell layer associated PG was modified with a decrease in HSPG and a correlative increase in CSPG. Cholera toxin and dBcAMP also dramatically stimulated hyaluronan synthesis by possible phosphorylation induced activation of hyaluronan synthase(s). 相似文献
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Background and aimAβ1−42 is an amyloidogenic peptide found within senile plaques extracted from those who died with a diagnosis of Alzheimer’s disease. The potent neurotoxicity of this peptide is related to its propensity to form aggregated conformations in vivo, a process that is influenced by the species and concentration of metal ions present within the local environment. This study examines the impact of different metals upon the early aggregatory behaviour and size of Aβ1−42 under simulated physiological conditions.MethodsThe size and aggregatory behaviour of Aβ1−42 in the presence and absence of metal ions was monitored during the initial 30 min of fibril formation in real-time using dynamic light scattering.ResultsIntensity scattering measurements showed a clear tendency towards aggregation with regards to Aβ1−42 only solutions (10 μM). Both equimolar Al3+ & Cu2+ lowered and stabilised the dimensions of Aβ1−42 aggregates; however, a diminutive but significant increase in size was still observed over a 30-min period. While excess Al3+ continued to supress the size of Aβ1−42, a 10-fold increase in the concentration of Cu2+ accelerated peptide aggregation relative to that observed for equimolar metal but not compared to Aβ1−42 alone.ConclusionThese results infer that Al3+ ions stabilise and aid in the maintenance of smaller, toxic intermediates while excess Cu2+ facilitates the formation of larger, more inert, amorphous species exceeding 1 μm in size. Furthermore, we propose that metal-induced toxicity of Aβ1−42 is reflective of their ability to preserve smaller oligomeric species in vitro. 相似文献
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《Molecular & cellular proteomics : MCP》2022,21(11):100418
Importin β1 (KPNB1) is a nucleocytoplasmic transport factor with critical roles in both cytoplasmic and nucleocytoplasmic transport, hence there is keen interest in the characterization of its subcellular interactomes. We found limited efficiency of BioID in the detection of importin complex cargos and therefore generated a highly specific and sensitive anti-KPNB1 monoclonal antibody to enable biotinylation by antibody recognition analysis of importin β1 interactomes. The monoclonal antibody recognizes an epitope comprising residues 301-320 of human KPBN1 and strikingly is highly specific for cytoplasmic KPNB1 in diverse applications, with little reaction with KPNB1 in the nucleus. Biotinylation by antibody recognition with this novel antibody revealed numerous new interactors of importin β1, expanding the KPNB1 interactome to cytoplasmic and signaling complexes that highlight potential new functions for the importins complex beyond nucleocytoplasmic transport. Data are available via ProteomeXchange with identifier PXD032728. 相似文献
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Steven J. Tucker David McClelland Kristina Sep?i? Roderick H. Scott 《生物化学与生物物理学报:生物膜》2003,1614(2):171-181
The ability of two alkyl pyridinium sponge toxin preparations (poly-APS and halitoxin) to form transient pores/lesions in cell membranes and allow transfection of plasmid cDNA have been investigated using HEK 293 cells. Poly-APS and halitoxin preparations caused a collapse in membrane potential, reductions in input resistance and increased Ca2+ permeability. At least partial recovery was observed after poly-APS application but recovery was more rarely seen with halitoxin. The transfection with plasmid cDNAs for an enhanced green fluorescent protein (EGFP) and human tumour necrosis factor receptor 2 (TNFR2) was assessed for both toxin preparations and compared with lipofectamine. Stable transfection was achieved with poly-APS although it was less efficient than lipofectamine. These results show that viable cells transfected with alien cDNA can be obtained using novel transient pore-forming alkyl pyridinium sponge toxins and a simple pre-incubation protocol. This provides the first proof of principle that pore-forming alkyl pyridinium compounds can be used to deliver cDNA to the intracellular environment without permanently compromising the plasma membrane. 相似文献
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We have investigated the ability of a series of synthetic vasopressin analogues and related peptides to compete with (3H)-arginine8 vasopressin for binding sites in rat renal medulla and dorsal hindbrain. In renal medulla, arginine8 vasopressin and deamino arginine8 vasopressin, a selective antidiuretic, were equipotent while two antagonists of the pressor action of arginine vasopressin were less potent. In the dorsal hindbrain, arginine8 vasopressin and the pressor antagonists were more potent than the synthetic antidiuretic. Potency profiles of these and other analogues suggest that the renal medulla and dorsal hindbrain vasopressin receptors represent different subtypes. 相似文献