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排序方式: 共有222条查询结果,搜索用时 15 毫秒
71.
Matthews JM Qin N Colburn RW Dax SL Hawkins M McNally JJ Reany L Youngman MA Baker J Hutchinson T Liu Y Lubin ML Neeper M Brandt MR Stone DJ Flores CM 《Bioorganic & medicinal chemistry letters》2012,22(8):2922-2926
A series of benzothiophene-based phosphonates was synthesized and many analogs within the series were shown to be potent antagonists of the TRPM8 channel. The compounds were obtained as a racemic mixture in 5 synthetic steps, and were tested for TRPM8 antagonist activity in a recombinant, canine TRPM8-expressing cell line using a fluorometric imaging plate reader (FLIPR) assay. Structure-activity relationships were developed initially by modification of the core structure and subsequently by variation of the aromatic substituents and the phosphonate ester. Compound 9l was administered intraperitoneally to rats and demonstrated engagement of the TRPM8 target in both prevention and reversal-modes in an icilin-induced 'wet-dog' shake model. 相似文献
72.
G. Park F. H. Lu N. Ye M. W. Brechbiel S. V. Torti F. M. Torti R. P. Planalp 《Journal of biological inorganic chemistry》1998,3(5):449-457
The interaction of Fe(II) and Fe(III) with the novel Fe(II) chelator N,N′N″-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane (referred to as tachpyr) gives rise to six-coordinate, low-spin, cationic complexes of Fe(II).
Tachpyr also displays a cytotoxicity toward cultured bladder cancer cells that is believed to involve coordination of intracellular
iron. The anaerobic reaction of tachpyr with Fe(II) salts affords the Fe(II)-tachpyr2+ complex, but in presence of oxygen, oxidative dehydrogenation of one or two of the aminomethylene group(s) of the ligand
occurs, with formal loss of H2: R—N(H)—C(H)2—(2-py) → R—N=C(H)—(2-py)+H2. The resulting mono- and diimino Fe(II) complexes (denoted as [Fe(tachpyr-H2)]2+ and [Fe(tachpyr-2H2)]2+) are an inseparable mixture, but they may be fully oxidized by H2O2 to the known tris(imino) complex Fe(II)[cis,cis-1,3,5-tris(pyridine-2-carboxaldimino)cyclohexane]2+ (or [Fe(tachpyr-3H2)]2+). Cyclic voltammetry of the imino complex mixture reveals an irreversible anodic wave at +0.78 V vs. NHE. Tachpyr acts as
a reducing agent toward Fe(IIII) salts, affording the same two Fe(II) imino complexes as products. Tachpyr also reductively
removes Fe(III) from an Fe(III)(ATP)3 complex (which is a putative form of intracellular iron), producing the two Fe(II) imino complexes. Novel N-alkylated derivatives of tachpyr have been synthesized. N-Alkylation has two effects on tachpyr: lowering metal affinity through increased steric hindrance, and preventing Fe(III)
reduction because oxidative dehydrogenation of nitrogen is blocked. The N-methyl tachpyr derivative binds Fe(II) only weakly as a high-spin complex, and no complexation or reduction of Fe(III) is
observed. Corresponding to their inability to bind iron, the N-alkylated chelators are nontoxic to cultured bladder cancer cells. A tach-based chelator with three N-propyleneamino arms is also synthesized. Studies of the chemical and biochemical properties of this chelator further support
a relationship between intracellular iron chelation, iron reduction, and cytotoxicity.
Received: 23 March 1998 / Accepted: 1 June 1998 相似文献
73.
Yoshiaki Tsuji Jun Ninomiya-Tsuji Suzy V. Torti Frank M. Torti 《Experimental cell research》1993,209(2)
Normal human diploid fibroblasts undergo a finite number of doublings in culture. This process of senescence is accompanied by a loss in the ability to respond to proliferative stimuli and is therefore distinct from the quiescent state induced by nutrient deprivation. We have studied changes in gene expression induced in these cells following exposure to the cytokine, tumor necrosis factor-α (TNF). We observed that TNF induced CDC2 and CDK2 expression in early-passage quiescent WI-38 fibroblasts. However, as cells approached senescence, their ability to induce CDC2 and CDK2, as well as stimulate DNA synthesis in response to TNF, progressively declined, with minimal to absent induction in senescent cells. This occurred despite the TNF-dependent induction of such proliferation-independent genes as manganese superoxide dismutase and interleukin-6 in senescent and quiescent cells. Serum was similarly unable to induce CDC2 or CDK2 expression in senescent cells. These results demonstrate that senescent cells are selectively deficient in TNF-mediated induction of CDC2 and CDK2, genes crucial to DNA synthesis and mitosis. 相似文献
74.
Cloning and sequencing of a gene encoding carminomycin 4-O-methyltransferase from Streptomyces peucetius and its expression in Escherichia coli. 总被引:7,自引:7,他引:0
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Sequence analysis of a portion of the Streptomyces peucetius daunorubicin biosynthetic gene cluster revealed a complete open reading frame (dnrK) that showed DNA and protein sequence homology to several O-methyltransferases. Expression of dnrK in Streptomyces lividans and Escherichia coli was done to show that this gene codes for carminomycin 4-O-methyltransferase. The deduced carminomycin 4-O-methyltransferase protein shows a conserved nucleotide binding site for its S-adenosyl-L-methionine cofactor. 相似文献
75.
Ventricular alpha 1-adrenergic receptor concentration, measured by specific binding of [3H]-prazosin, decreases by 33% as rats age from 3 to 24 months. No age changes occur in binding affinity for [3H]-prazosin or potency of various alpha-adrenergic agonists and antagonists to displace [3H]-prazosin. The ratio of membrane protein to ventricular wet weight also does not change significantly with age. These results suggest a possible mechanism for loss of cardiovascular alpha-adrenergic responsiveness during aging. 相似文献
76.
1,2-O-Alkylidene-β-l-idofuranurono-6,3-lactones were obtained from the corresponding 5-O-toluene-p-sulphonyl-α-d-glucofuranurono-6,3-lac tones by a sequence involving lactone reduction, benzoylation of HO-6, inversion of configuration at C-5, deacylation, and lactol oxidation. Hydrogenolysis or methanolysis of 1,2-O- benzylidene-β-l-idofuranurono-6,3-lactone gave l-idofuranurono-6,3-lactone and a mixture of its methyl glycosides, respectively. 相似文献
77.
Genetic characterization of a filament-forming, lipoprotein-deficient mutant of Escherichia coli. 总被引:4,自引:2,他引:2
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The fam-715 allele of Escherichia coli ST715, previously described as a temperature-sensitive filament former with reduced levels of lipoprotein at the nonpermissive temperature (S. V. Torti and J. T. Park, Nature [London] 263: 323--326, 1976), was mapped at 74 min. This mutation appears to be amber. It is recessive and can be complemented by F' plasmids carrying the wild-type allele or by an F' plasmid carrying an amber suppressor. Isotopic labeling experiments as well as map position differentiate the fam-715 allele from lipoprotein structural gene mutations. 相似文献
78.
Interleukin 1 induces ferritin heavy chain in human muscle cells 总被引:4,自引:0,他引:4
Y Wei S C Miller Y Tsuji S V Torti F M Torti 《Biochemical and biophysical research communications》1990,169(1):289-296
Interleukin 1 alpha (IL-1) and tumor necrosis factor alpha (TNF) are two monokines which play a prominent role in the response to inflammation and injury. We recently observed that TNF leads to an increase in the synthesis of the heavy chain of ferritin, suggesting that TNF may be involved in iron homeostasis (Torti et al. (1988) J. Biol. Chem. 263, 12638-12644). The experiments reported here demonstrate that in cultured human muscle cells, IL-1 induces ferritin H mRNA and protein as effectively as TNF. TNF and IL-1 were additive in their effects on ferritin H expression, and IL-1 induction of ferritin H was not blocked by anti-TNF antibodies. Ferritin H induction was a specific response not observed with beta or gamma interferon, nor with transforming growth factor beta. Both differentiated myotubes as well as myoblasts responded to IL-1 with the induction of ferritin H. These results suggest that monokine-mediated alterations in the subunit composition of the ferritin molecule may be of biological relevance in the response to inflammation and injury. 相似文献
79.
M Torti M F Crouch E G Lapetina 《Biochemical and biophysical research communications》1992,186(1):440-447
Using specific antibodies against the alpha subunit of the inhibitory GTP-binding protein Gi, we analyzed the association of Gi alpha with other cellular components in human platelets. Three tyrosine phosphorylated proteins with molecular mass of 63, 58, and 55 kDa were specifically associated with Gi alpha in resting platelets. Stimulation of platelets with epinephrine, but not with thrombin, induced an increase of the reactivity of the 63- and 55-kDa proteins to anti-phosphotyrosine antibodies on western blotting. By in vitro kinase assay we found that epinephrine induced the association of kinase activity with Gi alpha and that the 63-kDa protein was phosphorylated by this activity. The association of kinase activity with Gi alpha in epinephrine-stimulated platelets paralleled the association of pp60src with Gi alpha, as detected by western blotting analysis using specific anti-pp60src monoclonal antibodies. The interaction of pp60src with Gi alpha may play a role in the mechanism of platelet activation by epinephrine or in the epinephrine-induced potentiation of the action of other platelet agonists. 相似文献
80.
CpG Island microarray probe sequences derived from a physical library are representative of CpG Islands annotated on the human genome 总被引:8,自引:1,他引:7