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Lipoprotein nature of the colicin A lysis protein: effect of amino acid substitutions at the site of modification and processing. 总被引:19,自引:9,他引:10
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The colicin A lysis protein (Cal) is required for the release of colicin A to the medium by producing bacteria. This protein is produced in a precursor form that contains a cysteine at the cleavage site (-Leu-Ala-Ala-Cys). The precursor must be modified by the addition of lipid before it can be processed. The maturation is prevented by globomycin, an inhibitor of signal peptidase II. Using oligonucleotide-directed mutagenesis, the alanine and cystein residues in the -1 and +1 positions of the cleavage site were replaced by proline and threonine residues, respectively, in two different constructs. Both substitutions prevented the normal modification and cleavage of the protein. The marked activation of the outer membrane detergent-resistant phospholipase A observed with wild-type Cal was not observed with the Cal mutants. Both Cal mutants were also defective for the secretion of colicin A. In one mutant, the signal peptide appeared to be cleaved off by an alternative pathway involving signal peptidase I. Electron microscope studies with immunogold labeling of colicin A on cryosections of pldA and cal mutant cells indicated that the colicin remains in the cytoplasm and is not transferred to the periplasmic space. These results demonstrate that Cal must be modified and processed to activate the detergent-resistant phospholipase A and to promote release of colicin A. 相似文献
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L D'Agostino S Pignata B Daniele R Ventriglia G Ferrari C Ferraro S Spagnuolo P E Lucchelli G Mazzacca 《Biochimica et biophysica acta》1989,993(2-3):228-232
Plasma diamine oxidase (DAO) values are enhanced by intravenous injection of heparin which releases the enzyme, synthesized in small bowel enterocytes, from binding sites located on endothelial cells of the intestinal microvasculature. Intestinal DAO, in analogy with lipoprotein lipase (another heparin-released enzyme), is believed to be electrostatically linked to endothelial binding sites composed of a glycosaminoglycan (GAG) which is presumably heparan sulphate, but the complete mechanism of enzyme release is not known. In this study we assayed in rats the DAO-releasing capability of heparan sulphate, dermatan sulphate, chondroitin sulphate A and hyaluronic acid, all heparin related compounds. Heparan sulphate, a compound with the same hexosamine as heparin but with a lower concentration of sulphated iduronic acid, induced a very high release of DAO (3-fold less than heparin), while the other tested GAGs, composed of higher proportions of non sulphated uronic acid and with galactosamine instead of glucosamine, induced a significantly lower release. In rats treated with 60 mg heparan sulphate the significant decrease in ileal mucosal DAO activity indicates that, in analogy with heparin, the high plasma enzymatic activity induced is of enterocytic origin. It is suggested that the high charge density of the compounds tested, due to the degree of sulphatation, is the decisive factor in promoting the release of intestinal DAO. 相似文献
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Correction of mouse ornithine transcarbamylase deficiency by gene transfer into the germ line 总被引:2,自引:0,他引:2
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C Cavard G Grimber N Dubois J F Chasse M Bennoun M Minet-Thuriaux P Kamoun P Briand 《Nucleic acids research》1988,16(5):2099-2110
The sparse fur with abnormal skin and hair (Spf-ash) mouse is a model for the human X-linked hereditary disorder, ornithine transcarbamylase (OTC) deficiency. In Spf-ash mice, both OTC mRNA and enzyme activity are 5% of control values resulting in hyperammonemia, pronounced orotic aciduria and an abnormal phenotype characterized by growth retardation and sparse fur. Using microinjection, we introduced a construction containing rat OTC cDNA linked to the SV40 early promoter into fertilized eggs of Spf-ash mice. The expression of the transgene resulted in the development of a transgenic mouse whose phenotype and orotic acid excretion are fully normalized. Thus, the possibility of correcting hereditary enzymatic defect by gene transfer of heterologous cDNA coding for the normal enzyme has been demonstrated. 相似文献
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Daniele Arobba Andrea Quaglia Paolo Panagia Paolo Minuti Sergio Innocenti Pier Luigi Odda 《Aerobiologia》1988,4(1-2):38-46
Riassunto Sono state rilevate durante un monitoraggio aerobiologico effettuato a Pietra Ligure (Savona) nel corso del 1987 le concentrazioni
polliniche di 50 taxa ed è stata valutata l'influenza relativa dei fattori meteorologici. Le osservazioni palinologiche sono
state rapportate alle concentrazioni sieriche delle IgE specifiche, alla reattività bronchiale specifica ed aspecifica valutate
in 101 pazienti allergici (rinitici ed asmatici), sensibilizzati a Graminaceae ed Urticaceae (Parietaria) al fine di riconoscere
correlazioni tra le caratteristiche aerobiologiche di questi allergeni edi meccanismi patogenetici che sostengono la reattività
bronchiale.
相似文献
8.
Arsenio Corrado Negrini Renato Ariano Guiseppina Delbono Antonio Ebbli Antonio Quaglia Daniele Arobba 《Aerobiologia》1992,8(3):355-358
Summary The authors examined 734 sensitised patients living in four localities in Liguria (Genoa, Savona, Pietra Ligure and Sanremo). The commonest source of sensitisation (62.7%) was Urticaceae (Parietaria), followed by Poaceae (52.5%) andOlea europaea L. (24.0%). A survey of airborne pollens revealed a greater presence of Urticaceae and Poaceae in Genoa and of Oleaceae in Pietra Ligure and Sanremo. 相似文献
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A molecular, genetic and immunological approach to the functioning of colicin A, a pore-forming protein 总被引:14,自引:0,他引:14
D Cavard V Crozel J P Gorvel F Pattus D Baty C Lazdunski 《Journal of molecular biology》1986,187(3):449-459
We have constructed, by recombinant DNA techniques, one hybrid protein, colicin A-beta-lactamase (P24), and two modified colicin As, one (P44) lacking a large central domain and the other (PX-345) with a different C-terminal region. The regulation of synthesis, the release into the medium and the properties of these proteins were studied. Only P44 was released into the medium. This suggests that both ends of the colicin A polypeptide chain might be required for colicin release. None of the three proteins was active on sensitive cells in an assay in vivo. However, P44 was able to form voltage-dependent channels in phospholipid planar bilayers. Its lack of activity in vivo is therefore probably caused by the inability to bind to the receptor in the outer membrane. PX-345 is a colicin in which the last 43 amino acids of colicin A have been replaced by 27 amino acids encoded by another reading frame in the same region of the colicin A structural gene; it was totally unable to form pores in planar bilayers at neutral pH but showed a very slight activity at acidic pH. These results confirm that the C-terminal domain of colicin A is involved in pore formation and indicate that at least the 43 C-terminal amino acid residues of this domain play a significant role in pore formation or pore function. Fifteen monoclonal antibodies directed against colicin A have been isolated by using conventional techniques. Five out of the 15 monoclonal antibodies could preferentially recognize wild-type colicin A. In addition, the altered forms of the colicin A polypeptide were used to map the epitopes of ten monoclonal antibodies reacting specifically with colicin A. Some of the antibodies did not bind to colicin A when it was pre-incubated at acidic pH suggesting that colicin A undergoes conformational change at about pH 4. The effects of monoclonal antibodies on activity in vivo of colicin A were investigated. The degree of inhibition observed was related to the location of the epitopes, with monoclonal antibodies reacting with the N terminus giving greater inhibition. The monoclonal antibodies directed against the C-terminal region promoted an apparent activation of colicin activity in vivo. 相似文献