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101.
102.
Epidermal growth factor receptor tyrosine kinase phosphorylation of glucose-6-phosphate dehydrogenase in vitro 总被引:1,自引:0,他引:1
M A Napier M T Lipari R G Courter C H Cheng 《Archives of biochemistry and biophysics》1987,259(2):296-304
The specific tyrosine phosphorylation of glucose-6-phosphate dehydrogenase (G6PDH) by the epidermal growth factor (EGF) receptor in vitro is demonstrated. The Km values of the substrate G6PDH and of ATP for the receptor tyrosine kinase were ca. 1 and 10 microM, respectively. The rate of phosphorylation was EGF dependent, with a four-fold increase in Vmax in the presence of EGF. The phosphorylation was stimulated maximally by 0.2 microM or greater EGF, with an ED50 of ca. 20 nM which is consistent with the affinity of the solubilized receptor for EGF. Using conditions of 5 microM G6PDH, 100 microM ATP, 5 mM Mg2+, and 1 mM Mn2+, up to 0.3 mol phosphate was incorporated into 1 mol of the 55-kDa subunit of Baker's yeast G6PDH. Tryptic peptide mapping revealed several unique phosphopeptides for both Baker's yeast and bovine adrenal G6PDH. The patterns of phosphopeptides for a given enzyme were identical for basal and EGF-stimulated phosphorylation. 相似文献
103.
The teleost Fundulus heteroclitus (L.) possesses two loci, Gpi-A and Gpi-B,
for the glycolytic enzyme, glucose-phosphate isomerase (GPI; D-
glucose-6-phosphate ketol-isomerase; E.C. 5.3.1.9). The Gpi-B locus is
polymorphic in Fundulus, with two common alleles, Gpi-Bb and Gpi-Bc,
distributed in a clinal manner in populations along the east coast of North
America. Since this clinal distribution is strongly correlated with a
temperature gradient, we asked whether the GPI-B2 allozymes were
functionally adapted to the thermal environment in which a given phenotype
predominated. The two major GPI-B2 allozymes were purified to homogeneity
and were characterized as to molecular weight, isoelectric pH, thermal
denaturation, and kinetic parameters. Both GPI-Bb2 and GPI- Bc2 allozymes
have molecular masses of 110 kD, and they have isoelectric pHs of 6.4 and
6.6, respectively. The GPI-Bb2 allozyme was more stable to thermal
denaturation than was the GPI-Bc2 enzyme. Kinetic properties of the allelic
isozymes were investigated both as a function of pH and as a function of
temperature. At 25 degrees C, over the pH range considered, there were no
significant differences between allozymes, either in Km for
fructose-6-phosphate or in Ki for 6- phosphogluconate, but apparent Vmax
values differed between pH 7.5 and pH 8.5. All steady-state kinetic
parameters showed strong temperature dependence, but the allozymes differed
only in the Ki for 6- phosphogluconate at temperatures greater than 30
degrees C. On the basis of the observed structural and functional
differences alluded to above, the hypothesis that the major allelic
isozymes of the Gpi-B locus were functionally equivalent was rejected.
However, it is not yet known whether these structural and functional
differences have any significance at higher levels of biological
organization.
相似文献
104.
105.
Pickett JA Birkett MA Bruce TJ Chamberlain K Gordon-Weeks R Matthes MC Napier JA Smart LE Woodcock CM 《Phytochemistry》2007,68(22-24):2937-2945
The challenges and opportunities for protecting agricultural production of food and other materials will be met through exploiting the induction of defence pathways in plants to control pests, diseases and weeds. These approaches will involve processes that can be activated by application of natural products, patented in terms of this use, to "switch on" defence pathways. Already, a number of secondary metabolite defence compounds are known for which the pathways are conveniently clustered genomically, e.g. the benzoxazinoids (hydroxamic acids) and the avenacins. For the former, it is shown that the small molecular weight lipophilic activator cis-jasmone can induce production of these compounds and certain genes within the pathway. Numerous groups around the world work on inducible defence systems. The science is rapidly expanding and involves studying the interacting components of defence pathways and the switching mechanisms activated by small molecular weight lipophilic compounds. Examples are described of how plant breeding can exploit these systems and how heterologous gene expression will eventually give rise to a new range of GM crops for food and energy, without the need for external application of synthetic pesticides. 相似文献
106.
107.
Neil Moss Younggi Choi Derek Cogan Adam Flegg Andreas Kahrs Pui Loke Orietta Meyn Raj Nagaraja Spencer Napier Ashley Parker J. Thomas Peterson Philip Ramsden Christopher Sarko Donna Skow Josh Tomlinson Heather Tye Mark Whitaker 《Bioorganic & medicinal chemistry letters》2009,19(8):2206-2210
We have been exploring the potential of 5-HT2B antagonists as a therapy for chronic heart failure. To assess the potential of this therapeutic approach, we sought compounds possessing the following attributes: (a) potent and selective antagonism of the 5-HT2B receptor, (b) low impact of serum proteins on potency, and (c) desirable pharmacokinetic properties. This Letter describes our investigation of a biphenyl benzimidazole class of compounds that resulted in 5-HT2B antagonists possessing the above attributes. Improving potency in a human serum albumin shift assay proved to be the most significant SAR discovery. 相似文献
108.
109.
Nichole Cerutti Barry V. Mendelow Grant B. Napier Maria A. Papathanasopoulos Mark Killick Makobetsa Khati Wendy Stevens Alexio Capovilla 《The Journal of biological chemistry》2010,285(33):25743-25752
HIV-1 enters cells via interaction between the trimeric envelope (Env) glycoprotein gp120/gp41 and the host cell surface receptor molecule CD4. The requirement of CD4 for viral entry has rationalized the development of recombinant CD4-based proteins as competitive viral attachment inhibitors and immunotherapeutic agents. In this study, we describe a novel recombinant CD4 protein designed to bind gp120 through a targeted disulfide-exchange mechanism. According to structural models of the gp120-CD4 receptor complex, substitution of Ser60 on the CD4 domain 1 α-helix with Cys positions a thiol in proximity of the gp120 V1/V2 loop disulfide (Cys126–Cys196), satisfying the stereochemical and geometric conditions for redox exchange between CD4 Cys60 and gp120 Cys126, and the consequent formation of an interchain disulfide bond. In this study, we provide experimental evidence for this effect by describing the expression, purification, refolding, receptor binding and antiviral activity analysis of a recombinant two-domain CD4 variant containing the S60C mutation (2dCD4-S60C). We show that 2dCD4-S60C binds HIV-1 gp120 with a significantly higher affinity than wild-type protein under conditions that facilitate disulfide exchange and that this translates into a corresponding increase in the efficacy of CD4-mediated viral entry inhibition. We propose that targeted redox exchange between conserved gp120 disulfides and nucleophilic moieties positioned strategically on CD4 (or CD4-like scaffolds) conceptualizes a new strategy in the development of high affinity HIV-1 Env ligands, with important implications for therapy and vaccine development. More generally, this chalcogen substitution approach provides a general means of stabilizing receptor-ligand complexes where the structural and biophysical conditions for disulfide exchange are satisfied. 相似文献
110.