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41.
Arginine kinase displays a distinctive rise and fall in specific activity and specific protein levels during the prepupal stage of Drosophila development with maximal activity occurring at morphological stage P3. This developmentally regulated peak is under the influence of ecdysone. Altered doses of the major ecdysone-inducible "early" genes at cytological regions 75B and 2B5 alter this pattern of expression while altered doses of another major "early" gene at 74EF have no effect. We hypothesize that a product of the 2B5 locus and a product of the 75B locus interact to effect this developmental pattern of expression of Drosophila arginine kinase. 相似文献
42.
Anthrax toxin protective antigen: low-pH-induced hydrophobicity and channel formation in liposomes 总被引:10,自引:2,他引:8
To probe the role of the protective antigen (PA) component of anthrax toxin in toxin entry into animals cells, we examined the membrane channel-forming properties and hydrophobicity of intact and trypsin-cleaved forms of the protein at various pH values. At neutral pH neither form caused release of entrapped K+ from unilamellar lipid vesicles. At pH values below 6.0, however, K+ was rapidly released upon addition of either the nicked PA (PAN) or the 63 kDa tryptic fragment of PA (PA63), which has been implicated in the toxin entry process. Under the same conditions intact PA exhibited only weak channel-forming activity, and PA20, the complementary tryptic fragment, showed no such activity. Both PA and PA63 exhibited enhanced hydrophobicity at acidic pH values, but the enhancement was greater and the pH threshold higher with PA63. Our findings indicate that proteolytic removal of PA20 from intact PA enables the residual protein, PA63, to adopt a conformation at mildly acidic pH values that permits it to insert readily and form channels in membranes. Thus acidic conditions within endocytic vesicles may trigger membrane insertion of PA63, which in turn promotes translocation of ligated effector moieties, edema factor or lethal factor, across the vesicle membrane into the cytosol. 相似文献
43.
Arginine kinase displays a distinctive rise and fall in specific activity and specific protein levels during the prepupal stage of Drosophila development with maximal activity occurring at morphological stage P3. This developmentally regulated peak is under the influence of ecdysone. Altered doses of the major ecdysone-inducible “early” genes at cytological regions 75B and 2B5 alter this pattern of expression while altered doses of another major “early” gene at 74EF have no effect. We hypothesize that a product of the 2B5 locus and a product of the 75B locus interact to effect this developmental pattern of expression of Drosophila arginine kinase. © 1992 Wiley-Liss, Inc. 相似文献
44.
Effect of length, supercoiling, and pH on intramolecular triplex formation. Multiple conformers at pur.pyr mirror repeats 总被引:8,自引:0,他引:8
The conformations adopted by five oligopurine.oligopyrimidine (pur.pyr) inserts of various lengths and sequence repeats in recombinant plasmids were evaluated as a function of pH and negative super-helicaldensity. Patterns of chemical reactivity (OsO4 and diethylpyrocarbonate) indicate that long (greater than 36 base pairs) pur.pyr segments can adopt intramolecular triplexes and that increasing the length of the pur.pyr tract reduces the dependence on low pH for structure formation, such that (GA)37 adopts an intramolecular triplex under moderate levels of negative superhelical stress (-sigma = 0.049) at neutral pH. This demonstrates that long pur.pyr segments, which are abundant in eukaryotic genomes, have the potential to adopt triplexes in vivo. Two-dimensional gel electrophoresis of the plasmids combined with chemical probing indicates that for longer sequences, multiple conformers of the intramolecular triplex exist at low pH. These conformers result from nucleation at various positions on the polypurine stretch, giving rise to different extents of relaxation at the same linking number. In addition, the metal ions Co2+, Mn2+, and Mg2+ have profound effects on the pattern of chemical reactivity displayed by long pur.pyr segments at both neutral and low pH, indicating that quite different structures may form in the presence of divalent metal ions. Thus, the types and extent of unusual structures adopted by long pur.pyr segments are complex and heterogeneous, and are dependent on pH, supercoiling, and the presence of divalent cations. 相似文献
45.
Summary Mutant strains of the mossPhyscomitrella patens that were resistant to the antibiotics streptomycin and chloramphenicol were isolated following UV irradiation. Mutants resistant
to streptomycin at 1.7×10−4
M showed both dominant and recessive Mendelian and inheritance patterns. Mutants resistant to streptomycin at 1.7 ¢ 10−4
M and to chloramphenicol at 3.1×10−4
M were, with one exception, cytoplasmically inherited. 相似文献
46.
P.J. Gardiner Julia L. Copas C. Schneider H.O.J. Collier 《Prostaglandins & other lipid mediators》1980,19(3):349-370
2-Decarboxy 2-hydroxymethyl prostaglandin E1 (TR4161) relaxed isolated guinea-pig trachea with about double and relaxed human isolated bronchial muscle with about one half the potency of PGE1. In conscious restrained cats an aerosol of TR4161 was about 100–1000 times less active than PGE1 in inducing tracheobronchial irritation. When given intravenously or by aerosol to the anaesthetised spontaneously breathing guinea-pig, TR4161 was approximately equipotent with PGE1 in inhibiting histamine-induced bronchoconstriction and in reducing basal inherent tone. The onset and duration of the bronchodilator effects of TR4161 administered intravenously, however, were significantly longer than those of PGE1. In conscious guinea-pigs, TR4161 by aerosol was approximately three times more potent than PGE1 in preventing histamine-induced convulsions, whereas only TR4161 was active in this test system when the test drugs were administered orally. These observations indicate that TR4161 might be therapeutically useful as a non-irritant prostaglandin bronchodilator in conditions of airway obstruction. 相似文献
47.
H.O.J. Collier Alison A. Francis Wendy J. McDonald-Gibson S.A. Saeed 《Prostaglandins & other lipid mediators》1976,11(2):219-225
Sulphasalazine (SZ) inhibits prostaglandin (PG) biosynthesis with a potency comparable to that of aceylsalicylate. The metabolites of SZ, sulphapyridine and 5-aminosalicylic acid, were of considerably lower potency as inhibitors of PG biosynthesis in the synthetase preparations used. The inhibition of prostaglandin production by SZ could at least partly account for the clinical utility of sulphasalazine in ulcerative colitis. Sulphapyridine may help to maintain inhibitory concentrations of SZ by restraining bacterial breakdown of the active drug. 相似文献
48.
Further evidence is given that dependence arises from the agonist action of opiates. From this and our previous propositions assigning a fundamental role to neuronal cyclic AMP in (i) the agonist action of opiates and (ii) the expression of the abstinence syndrome, it follows that opiate dependence is a state of heightened potential activity of a neuronal cyclic AMP mechanism, initiated and maintained by the blockade of an adenylate cyclase. Various possible mechanisms are discussed by which this potential is heightened. New evidence is given that morphine and naloxone stimulate prostaglandin biosynthesis without mutual antagonism. Preliminary evidence also is given that (i) the formation of cyclic AMP is enhanced in brain homogenates from heroin-dependent rats, and (ii) an acidified ethylacetate extract of brains of morphine-dependent rats induces quasi-abstinence effects when injected into a lateral cerebral ventricle of naive rats. 相似文献
49.
The paper re-examines, in the light of recent evidence, the original proposition that the ability of opiates to inhibit the stimulation by E prostaglandins of cyclic AMP formation in rat brain homogenate represents a biochemical mechanism that could account for the analgesic and allied effects of these drugs. It is concluded that subsequent evidence largely supports the original proposition; but that this can now be made more definite. It is proposed that inhibition of an adenylate cyclase of morphine-sensitive neurones is the decisive biochemical consequence of the binding of an opiate agonist with its specific receptor. 相似文献
50.
Binding stoichiometry and kinetics of the interaction of a human anthrax toxin receptor, CMG2, with protective antigen 总被引:8,自引:0,他引:8
Wigelsworth DJ Krantz BA Christensen KA Lacy DB Juris SJ Collier RJ 《The Journal of biological chemistry》2004,279(22):23349-23356
The protective antigen (PA) moiety of anthrax toxin binds to cellular receptors and mediates entry of the two enzymatic moieties of the toxin into the cytosol. Two PA receptors, anthrax toxin receptor (ATR)/tumor endothelial marker 8 (TEM8) and capillary morphogenesis protein 2 (CMG2), have been identified. We expressed and purified the von Willebrand A (VWA) domain of CMG2 and examined its interactions with monomeric and heptameric forms of PA. Monomeric PA bound a stoichiometric equivalent of CMG2, whereas the heptameric prepore form bound 7 eq. The Kd of the VWA domain-PA interaction is 170 pm when liganded by Mg2+, reflecting a 1000-fold tighter interaction than most VWA domains with their endogenous ligands. The dissociation rate constant is extremely slow, indicating a 30-h lifetime for the CMG2.PA monomer complex. CMG2 metal ion-dependent adhesion site (MIDAS) was studied kinetically and thermodynamically. The association rate constant (approximately 10(5) m(-1) s(-1)) is virtually identical in the presence or absence of Mg2+ or Ca2+ , but the dissociation rate of metal ion liganded complex is up to 4 orders of magnitude slower than metal ion free complex. Residual affinity (Kd approximately 960 nm) in the absence of divalent metal ions allowed the free energy for the contribution of the metal ion to be calculated as 5 kcal mol(-1), demonstrating that the metal ion-dependent adhesion site is directly coordinated by CMG2 and PA in the binding interface. The high affinity of the VWA domain for PA supports its potency in neutralizing anthrax toxin, demonstrating its potential utility as a novel therapeutic for anthrax. 相似文献