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401.
D. G. Smith D. R. Buckle A. Faller I. L. Pinto 《Bioorganic & medicinal chemistry letters》1992,2(12):1595-1598
A series of C-4 pyrrole substituted benzopyrans and benzopyranols has been prepared, some members of which are potent relaxants of guinea pig trachealis in vitro. These compounds appear to act via potassium channel opening. It is envisaged that a pyrrole ring substituted with an electron-withdrawing group can function as a bioisostere of the pyrrolidinone of cromakalim. Two tetracyclic derivatives have been also prepared, one of which (18) appears to act as a potassium channel activator in a similar manner to cromakalim while the other (15), although a potent relaxant of guinea pig trachealis, has a profile which is inconsistent with this mechanism of action. 相似文献
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D R Buckle J Bumstead G D Clarke K A Foster H Parr J F Taylor V E Thody R A Webster 《Prostaglandins, leukotrienes, and essential fatty acids》1988,33(1):29-33
A number of 2-benzylaminophenols, prepared from the corresponding 2-aminophenols by reductive alkylation, have been identified as highly potent inhibitors of 5-lipoxygenase with IC50 values in the nanomolar range. Most compounds were also shown to inhibit the release of the peptidoleukotrienes when administered intraperitoneally in a rat model of peritoneal anaphylaxis. Two compounds evaluated for their effects on anaphylactic contractions in isolated human lung were shown to attenuate the leukotriene-induced component of the response. 相似文献
404.
Sri Devi Sukumaran Shah Bakhtiar Nasir Jia Ti Tee Michael J. C. Buckle Rozana Othman Noorsaadah Abd. Rahman Vannajan Sanghiran Lee Syed Nasir Abbas Bukhari Chin Fei Chee 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):130
A series of C4-substituted tertiary nitrogen-bearing 2′-hydroxychalcones were designed and synthesised based on a previous mixed type acetylcholinesterase inhibitor. Majority of the 2′-hydroxychalcone analogues displayed a better inhibition against acetylcholinesterase (AChE) than butyrylcholinesterase (BuChE). Among them, compound 4c was identified as the most potent AChE inhibitor (IC50: 3.3 µM) and showed the highest selectivity for AChE over BuChE (ratio >30:1). Molecular docking studies suggested that compound 4c interacts with both the peripheral anionic site (PAS) and catalytic anionic site (CAS) regions of AChE. ADMET analysis confirmed the therapeutic potential of compound 4c based on its blood–brain barrier penetrating. Overall, the results suggest that this 2′-hydroxychalcone deserves further investigation into the therapeutic lead for Alzheimer’s disease (AD). 相似文献
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Background
Pelodera (Rhabditis) strongyloides is a small saprophytic nematode that lives in decaying organic matter. On rare occasions, it can invade the mammalian skin, causing a pruritic, erythematous, alopecic and crusting dermatitis on skin sites that come into contact with the ground. Diagnosis of the disease is based on case history (a dog living outdoors on damp straw bedding) with characteristic skin lesions and on the demonstration of typical larvae in skin scrapings or biopsy. Pelodera (rhabditic) dermatitis cases have been reported mainly from Central European countries and the United States. 相似文献407.
E. coli RNA polymerase, deleted in the C-terminal part of its alpha-subunit, interacts differently with the cAMP-CRP complex at the lacP1 and at the galP1 promoter. 总被引:8,自引:3,他引:5 下载免费PDF全文
A deletion of the C-terminal part of the alpha-subunit of RNA polymerase is known to affect differently promoters activated by CRP depending on the location of the CRP binding site at the promoter. When the CRP binding site is located at -61.5, as at lacP1 (a type I promoter), activation is strongly impaired while it is not significantly affected at galP1 where CRP binds 41.5 bp upstream of the start of the message (type II promoter). We have investigated the differences in the architecture of the corresponding open complexes by comparing the positioning of holoenzymes reconstituted respectively with native or with truncated alpha-subunits (containing the first 235 or 256 residues of a) at two 'up' promoter mutants of the lacP1 and galP1 promoters (respectively lacUV5 and gal9A16C). First, the affinity of wild-type RNA polymerase for both promoters is increased by the presence of CRP and cAMP. By contrast, holoenzymes reconstituted with truncated alpha-subunits, show cooperative binding at the galP1 promoter only. Second, footprinting data confirm these observations and indicate that the truncated holoenzymes are unable to recognize regions of the promoter upstream from position -40. The absence of contacts between the truncated enzymes and CRP at the lacP1 promoter can explain the deficiency in activation. At the galP1 promoter, where the CRP site is closer to the initiation site, protein-protein contacts can still occur with the truncated polymerases, showing that the C-terminal part of the alpha-subunit is not involved in activation. 相似文献
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