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131.
Masaki Asada Tetsuo Obitsu Atsushi Kinoshita Yoshihiko Nakai Toshihiko Nagase Isamu Sugimoto Motoyuki Tanaka Hiroya Takizawa Ken Yoshikawa Kazutoyo Sato Masami Narita Shuichi Ohuchida Hisao Nakai Masaaki Toda 《Bioorganic & medicinal chemistry letters》2010,20(8):2639-2643
A series of novel N-acylsulfonamide analogs were synthesized and evaluated for their binding affinity and antagonist activity for the EP3 receptor subtype. Representative compounds were also evaluated for their inhibitory effect on PGE2-induced uterine contraction in pregnant rats. Among those tested, a series of N-acylbenzenesulfonamide analogs were found to be more potent than the corresponding carboxylic acid analogs in both the in vitro and in vivo evaluations. The structure activity relationships (SAR) are also discussed. 相似文献
132.
Hisashi Kato-Noguchi Madoka Yamamoto Kazuya Tamura Toshiaki Teruya Kiyotake Suenaga Yoshiharu Fujii 《Plant Growth Regulation》2010,60(2):127-131
Aqueous methanol extracts of rattail fescue (Vulpia myuros) inhibited the growth of roots and shoots of cress (Lepidium sativum), lettuce (Lactuca sativa), alfalfa (Medicago sativa), timothy (Phleum pratense), Digitaria sanguinalis and Lolium multiflorum. Increasing the extract concentration increased the inhibition, suggesting that rattail fescue may have growth inhibitory
substances and possess allelopathic potential. The aqueous methanol extract of rattail fescue was purified and two main inhibitory
substances were isolated and identified by spectral data as (−)-3-hydroxy-β-ionone and (+)-3-oxo-α-ionol. Both substances
inhibited root and shoot growth of cress at concentrations greater than 0.3 μM. The concentrations required for 50% growth
inhibition on root and shoot growth of cress, lettuce, alfalfa, timothy, D. sanguinalis and L. multiflorum were 2.7–19.7 μM for (−)-3-hydroxy-β-ionone, and 2.1–34.5 μM for (+)-3-oxo-α-ionol. The concentration of (−)-3-hydroxy-β-ionone
and (+)-3-oxo-α-ionol, respectively, in rattail fescue was 7.8 and 3.7 μg g−1 fresh weight. Considering the endogenous level and the inhibitory activity, (−)-3-hydroxy-β-ionone and (+)-3-oxo-α-ionol
may work as allelopathic substances in rattail fescue through the growth inhibition of neighboring plant species. 相似文献
133.
Hidenori Takahashi Testuhito Shinkawa Shinjiro Nakai Yasunori Inoue 《Plant Growth Regulation》2010,62(2):137-149
Root hair formation is induced in lettuce seedlings when the seedlings are transferred from a liquid medium at pH 6.0 to one
at pH 4.0. Auxin, ethylene, and light are also required for the induction of root hair formation. To investigate the mechanism
by which ethylene production is regulated during root hair formation, we isolated three 1-aminocyclopropane-1-carboxylic acid
(ACC) oxidase genes (Ls-ACO1, 2, and 3) from lettuce, each of which exists as a single copy in the genome. Analysis of the deduced amino acid sequences of the three
ACO proteins as well as a phylogenetic analysis revealed that Ls-ACO3 was the most divergent among the ACO family. Northern
hybridization analyses revealed that the mRNA levels of Ls-ACO2, but not Ls-ACO1 and Ls-ACO3, increased in the primary root after the transfer to a pH 4.0 medium. Addition of ACC or indole-3-acetic acid (IAA) to the
pH 6.0 medium induced root hair formation, and a concomitant accumulation of Ls-ACO2 mRNA was observed. In contrast, the mRNA levels of Ls-ACO1 and Ls-ACO3 were unaffected by either ACC or IAA treatment. Furthermore, white light irradiation of dark-grown seedlings following the
transfer to pH 4.0 medium induced the accumulation of all three ACO mRNAs. However, accumulation of Ls-ACO2 mRNA was also observed in non-irradiated seedlings, suggesting that the expression of Ls-ACO2 was induced not by light but by low pH. These results suggest that among the differentially regulated ACO genes, Ls-ACO2 plays a key role in ethylene production during low-pH-induced root hair formation in lettuce. 相似文献
134.
135.
Emi Kamiyama Daisuke Nakai Tsuyoshi Mikkaichi Noriko Okudaira Osamu Okazaki 《Life sciences》2010,86(1-2):52-58
AimsThe inhibitory effect of angiotensin II type 1 receptor blockers (ARBs) on P-glycoprotein (P-gp) was examined to evaluate their clinical drug–drug interaction (DDI) potential.Main methodsWe performed an inhibition study on the vectorial transport of digoxin, a typical substrate for P-gp, using a human colonic adenocarcinoma cell line, Caco-2 cells, and verapamil-stimulated ATPase activity using human multidrug resistance 1 (hMDR1)-expressing membrane.Key findingsThe vectorial transport of digoxin was inhibited by candesartan cilexetil, irbesartan and telmisartan with the IC50 values of 14.7, 34.0 and 2.19 µM, respectively. Those values were 7.4–426-fold higher than their theoretical clinical gastrointestinal concentration [I] at doses in clinical DDI studies. Other ARBs failed to show interaction with P-gp.SignificanceIt was demonstrated that candesartan cilexetil, irbesartan and telmisartan had the potential to inhibit the transport of various drugs via P-gp. Telmisartan, which caused an increase in the serum digoxin concentration in humans, had a sufficiently high [I]/IC50 value, suggesting that DDI between digoxin and telmisartan was caused by the inhibition of digoxin efflux via intestinal P-gp. 相似文献
136.
A series of 2-phenylaliphatic-substituted androsta-1,4-diene-3,17-diones (6) as well as their androstenedione derivatives (5) were synthesized as aromatase inhibitors to gain insights of structure–activity relationships of varying the alkyl moiety (C1 to C4) of the 2-phenylaliphatic substituents as well as introducing a methyl- or trifluoromethyl function to p-position of a phenethyl moiety to the inhibitory activity. The inhibitors examined showed a competitive type inhibition. The 2-phenpropylandrosta-1,4-diene 6c was the most powerful inhibitor (Ki: 16.1 nM) among them. Compounds 6c along with the phenethyl derivative 6b caused a time-dependent inactivation of aromatase (kinact: 0.0293 and 0.0454 min?1 for 6b and 6c, respectively). The inactivation was prevented by the substrate androstenedione, and no significant effect of l-cysteine on the inactivation was observed in each case. Molecular docking of the phenpropyl compound 6c to aromatase was conducted to demonstrate that the phenpropyl group orients to a hydrophobic binding pocket in the active site to result in the formation of thermodynamically stable enzyme–inhibitor complex. 相似文献
137.
Madoka Koyanagi Julie A Kerns Linda Chung Yan Zhang Scott Brown Tudor Moldoveanu Harmit S Malik Mark Bix 《BMC evolutionary biology》2010,10(1):223
Background
Interleukin-4 (IL4) is a secreted immunoregulatory cytokine critically involved in host protection from parasitic helminths [1]. Reasoning that helminths may have evolved mechanisms to antagonize IL4 to maximize their dispersal, we explored mammalian IL4 evolution. 相似文献138.
Follow-up testing of rodent carcinogens not positive in the standard genotoxicity testing battery: IWGT workgroup report 总被引:1,自引:0,他引:1
Kasper P Uno Y Mauthe R Asano N Douglas G Matthews E Moore M Mueller L Nakajima M Singer T Speit G;IWGT Workgroup 《Mutation research》2007,627(1):106-116
At the Plymouth Third International Workshop on Genotoxicity Testing in June 2002, a new expert group started a working process to provide guidance on a common strategy for genotoxicity testing beyond the current standard battery. The group identified amongst others "Follow-up testing of tumorigenic agents not positive in the standard genotoxicity test battery" as one subject for further consideration [L. Müller, D. Blakey, K.L. Dearfield, S. Galloway, P. Guzzie, M. Hayashi, P. Kasper, D. Kirkland, J.T. MacGregor, J.M. Parry, L. Schechtman, A. Smith, N. Tanaka, D. Tweats, H. Yamasaki, Strategy for genotoxicity testing and stratification of genotoxicity test results-report on initial activities of the IWGT Expert Group, Mutat. Res. 540 (2003) 177-181]. A workgroup devoted to this topic was formed and met on September 9-10, 2005, in San Francisco. This workgroup was devoted to the discussion of when it would be appropriate to conduct additional genetic toxicology studies, as well as what type of studies, if the initial standard battery of tests was negative, but tumor formation was observed in the rodent carcinogenicity assessment. The important role of the standard genetic toxicology testing to determine the mode of action (MOA) for carcinogenesis (genotoxic versus non-genotoxic) was discussed, but the limitations of the standard testing were also reviewed. The workgroup also acknowledged that the entire toxicological profile (e.g. structure-activity relationships, the nature of the tumor finding and metabolic profiles) of a compound needed to be taken into consideration before the conduct of any additional testing. As part of the meeting, case studies were discussed to understand the practical application of additional testing as well as to form a decision tree. Finally, suitable additional genetic toxicology assays to help determine the carcinogenic MOA or establish a weight of evidence (WOE) argument were discussed and formulated into a decision tree. 相似文献
139.
140.
Design and synthesis of new potent dipeptidyl peptidase IV inhibitors with enhanced ex vivo duration
Kondo T Nekado T Sugimoto I Ochi K Takai S Kinoshita A Tajima Y Yamamoto S Kawabata K Nakai H Toda M 《Bioorganic & medicinal chemistry》2007,15(7):2631-2650
A series of 5beta-methylprolyl-2-cyanopyrrolidine analogs were synthesized and evaluated as DPP-IV inhibitors, and the duration of their ex vivo activity was assessed. Comparison of their potency and duration of action was done among three different species. The mode of binding was investigated, and the effect on the plasma glucose level was evaluated. Structure-activity relationships are also presented. 相似文献