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排序方式: 共有251条查询结果,搜索用时 15 毫秒
71.
Darby Schmidt Abigail Smenton Subharekha Raghavan Ester Carballo-Jane Silvi Lubell Tanya Ciecko Tom G. Holt Michael Wolff Andrew Taggart Larissa Wilsie Mihajlo Krsmanovic Ning Ren Daniel Blom Kang Cheng Peggy E. McCann M. Gerard Waters James Tata Steven Colletti 《Bioorganic & medicinal chemistry letters》2009,19(16):4768-4772
Niacin is an effective drug for raising HDL cholesterol and reducing coronary risks, but patients show low compliance with treatment due to severe facial flushing upon taking the drug. A series of bicyclic pyrazole carboxylic acids were synthesized and tested for their ability to activate the niacin receptor. One analog, 23, showed improved potency and lacked flushing at doses that effectively altered the lipid profile of rats. 相似文献
72.
Kevin NJ Duffy JL Kirk BA Chapman KT Schleif WA Olsen DB Stahlhut M Rutkowski CA Kuo LC Jin L Lin JH Emini EA Tata JR 《Bioorganic & medicinal chemistry letters》2003,13(22):4027-4030
HIV-1 protease inhibitors (PI) with an N-arylpyrrole moiety in the P(3) position afforded excellent antiviral potency and substantially improved aqueous solubility over previously reported variants. The rapid in vitro clearance of these compounds in human liver microsomes prompted oral coadministration with indinavir to hinder their metabolism by the cyctochrome P450 3A4 isozyme and allow for in vivo PK assessment. 相似文献
73.
Tata JR 《Nature reviews. Molecular cell biology》2002,3(9):702-710
A century ago, secretions from the pancreas were described as 'hormones', which we now know are secreted from all ductless glands. The development of various technologies has already contributed a great deal -- and will undoubtedly offer more -- to our understanding of their mode of action. 相似文献
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75.
Biagioni S Tata AM De Jaco A Augusti-Tocco G 《The International journal of developmental biology》2000,44(6):689-697
Development of the nervous system is dependent on the co-operation between cell determination events and the action of epigenetic factors; in addition to well known factors, e.g. growth factors, neurotransmitters have been assigned a role as "morphogens" and modulators of neuronal differentiation in an early developmental phase. The possible role of acetylcholine as a modulator of neuronal differentiation has been considered in two experimental systems. A neuroblastoma cell line, which does not synthesise any neurotransmitter, has been transfected with a choline acetyltransferase construct; activation of acetylcholine synthesis, thus achieved, is followed by a higher expression of neuronal specific traits. The presence in these cells of muscarinic receptors is consistent with the existence of an autocrine loop, which may be responsible for the more advanced differentiation state observed in the transfected cells. Expression of cholinergic markers appears as a common feature of DRG sensory neurons, independently of the neurotransmitter used. Choline acetyltransferase can be detected in DRG at early developmental stages. The distribution of muscarinic receptors in DRG has suggested that activation of acetylcholine synthesis may be related in an early developmental phase to the interaction between neurons and nonneuronal cells and to modulation of cell differentiation. Both systems suggest that acetylcholine may have a role as a modulator of neuronal differentiation. 相似文献
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77.
A mutant strain, KLAM59, of Pseudomonas aeruginosa has been isolated that synthesizes a catalytically inactive amidase. The mutation in the amidase gene has been identified
(Glu59Val) by direct sequencing of PCR-amplified mutant gene and confirmed by sequencing the cloned PCR-amplified gene. The
wild-type and altered amidase genes were cloned into an expression vector and both enzymes were purified by affinity chromatography
on epoxy-activated Sepharose 6B-acetamide followed by gel filtration chromatography. The mutant enzyme was catalytically inactive,
and it was detected in column fractions by monoclonal antibodies previously raised against the wild-type enzyme using an ELISA
sandwich method. The recombinant wild-type and mutant enzymes were purified with a final recovery of enzyme in the range of
70–80%. The wild-type and mutant enzymes behaved differently on the affinity column as shown by their elution profiles. The
molecular weights of the purified wild-type and mutant amidases were found to be 210,000 and 78,000 Dalton, respectively,
by gel filtration chromatography. On the other hand, the mutant enzyme ran as a single protein band on SDS-PAGE and native
PAGE with a M
r of 38,000 and 78,000 Dalton, respectively. These data suggest that the substitution Glu59Val was responsible for the dimeric
structure of the mutant enzyme as opposed to the hexameric form of the wild-type enzyme. Therefore, the Glu59 seems to be
a critical residue in the maintenance of the native quaternary structure of amidase. 相似文献
78.
Discovery and investigation of a novel class of thiophene-derived antagonists of the human glucagon receptor 总被引:1,自引:0,他引:1
Duffy JL Kirk BA Konteatis Z Campbell EL Liang R Brady EJ Candelore MR Ding VD Jiang G Liu F Qureshi SA Saperstein R Szalkowski D Tong S Tota LM Xie D Yang X Zafian P Zheng S Chapman KT Zhang BB Tata JR 《Bioorganic & medicinal chemistry letters》2005,15(5):1401-1405
A novel class of antagonists of the human glucagon receptor (hGCGR) has been discovered. Systematic modification of the lead compound identified substituents that were essential for activity and those that were amenable to further optimization. This SAR exploration resulted in the synthesis of 13, which exhibited good potency as an hGCGR functional antagonist (IC50 = 34 nM) and moderate bioavailability (36% in mice). 相似文献
79.
Summary Hydroxyurea inhibited growth of Pseudomonas aeruginosa strain AI 3 on media containing either acetanilide (N-phenyl acetamide) or acetamide as sole carbon sources. Mutants resistant to hydroxyurea inhibition of growth on acetanilide (OUCH strains) and acetamide (AmOUCH strains) displayed altered growth properties on various amide media compared with the parent strain AI 3. AI 3 amidase, which catalyses the initial step in the metabolism of acetanilide and acetamide, was inhibited by hydroxyurea in a time-dependent reaction that was slowly reversible at pH 7.2 Compared with AI 3 amidase, amidases from the OUCH mutants were much less sensitive to inhibition by hydroxyurea and showed altered substrate specificities and pH/activity profiles; amidases from the AmOUCH mutants were more sensitive to hydroxyurea inhibition but showed increased activity towards acetamide. Association of resistance to hydroxyurea inhibition with a mutation in the amidase structural gene of strain OUCH 4 was confirmed by transduction. 相似文献
80.