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排序方式: 共有331条查询结果,搜索用时 125 毫秒
31.
Erin Milner William McCalmont Jayendra Bhonsle Diana Caridha Dustin Carroll Sean Gardner Lucia Gerena Montip Gettayacamin Charlotte Lanteri ThuLan Luong Victor Melendez Jay Moon Norma Roncal Jason Sousa Anchalee Tungtaeng Peter Wipf Geoffrey Dow 《Bioorganic & medicinal chemistry letters》2010,20(4):1347-1351
Utilizing mefloquine as a scaffold, a next generation quinoline methanol (NGQM) library was constructed to identify early lead compounds that possess biological properties consistent with the target product profile for malaria chemoprophylaxis while reducing permeability across the blood–brain barrier. The library of 200 analogs resulted in compounds that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum. Herein we report selected chemotypes and the emerging structure–activity relationship for this library of quinoline methanols. 相似文献
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Perni RB Chandorkar G Cottrell KM Gates CA Lin C Lin K Luong YP Maxwell JP Murcko MA Pitlik J Rao G Schairer WC Van Drie J Wei Y 《Bioorganic & medicinal chemistry letters》2007,17(12):3406-3411
Reversible tetrapeptide-based compounds have been shown to effectively inhibit the hepatitis C virus NS3.4A protease. Inhibition of viral replicon RNA production in Huh-7 cells has also been demonstrated. We show herein that the inclusion of hydrogen bond donors on the P4 capping group of tetrapeptide-based inhibitors result in increased binding potency to the NS3.4A protease. The capping groups also impart significant effects on the pharmacokinetic profile of these inhibitors. 相似文献
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This paper describes the development of a new class of N-linked imidazoles as potential pH-sensitive, cleavable linkers for use in cancer drug delivery systems. Kinetic analysis of eight derivatives of N-ethoxybenzylimidazoles (NEBIs) showed that their rates of hydrolysis are accelerated in mild aqueous acidic solutions compared to in solutions at normal, physiological pH. Incorporation of electron donating or electron withdrawing substituents on the phenyl ring of the NEBI resulted in the ability to tune the rates of hydrolysis under mild acidic conditions with half-lives ranging from minutes to months. A derivative of NEBI carrying doxorubicin, a widely used anticancer agent, also showed an increased rate of hydrolysis under mild acid compared to that at normal physiological pH. The doxorubicin analogue resulting from hydrolysis from the NEBI exhibited good cytotoxic activity when exposed to human ovarian cancer cells. These results demonstrate a potentially useful, general strategy for conjugating a wide range of drugs to imidazole-containing delivery vessels via NEBI functionalities for controlled release of therapeutics for drug delivery applications. 相似文献
37.
Guanmei Wen Cheng Zhang Qishan Chen Le Anh Luong Arif Mustafa Shu Ye Qingzhong Xiao 《The Journal of biological chemistry》2015,290(31):19158-19172
Matrix metalloproteinase-8 (MMP8) has been shown to influence various cellular functions. As monocytes and macrophages (Mφ) express MMP8, we investigated if MMP8 played a role in macrophage differentiation and polarization. MMP8 expression was significantly increased during monocyte differentiation into Mφ. Monocyte-derived Mφ from MMP8-deficient mice expressed higher levels of M1-Mφ markers but lower levels of M2-Mφ markers than monocyte-derived Mφ from wild-type mice. Although Mφ from either MMP8-deficient or wild-type mice were inducible by interferon-γ into M1-Mφ, only wild-type Mφ but not MMP8-deficient Mφ could be induced into M2-Mφ by interleukin-4. However, MMP8-deficient Mφ exposed to conditioned culture media of wild-type Mφ developed a M2-Mφ phenotype. Compared with conditioned culture media of wild-type Mφ, conditioned culture media of MMP8-deficient Mφ contained a lower concentration of active transforming growth factor-β (TGF-β), an M2-Mφ inducer. Moreover, evidence also showed that the degradation of the TGF-β sequester, fibromodulin, was modulated by MMP8. The data indicate a previously unknown role of MMP8 in M2-Mφ polarization by cleaving fibromodulin and therefore increasing the bioavailability of the M2-Mφ inducer TGF-β. 相似文献
38.
Ni Y Gopalsamy A Cole D Hu Y Denny R Ipek M Liu J Lee J Hall JP Luong M Telliez JB Lin LL 《Bioorganic & medicinal chemistry letters》2011,21(19):5952-5956
We report here the synthesis and SAR of a new series of thieno[3,2-d]pyrimidines as potent Tpl2 kinase inhibitors. The proposed binding mode suggests the potential flipped binding mode depending on the substitution. Biacore studies show evidence of binding of these molecules to the protein kinase. The kinome inhibition profile of these molecules suggests good selectivity. 相似文献
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Luong MX Auerbach J Crook JM Daheron L Hei D Lomax G Loring JF Ludwig T Schlaeger TM Smith KP Stacey G Xu RH Zeng F 《Cell Stem Cell》2011,8(4):357-359
Human embryonic and induced pluripotent stem cell lines are being generated at a rapid pace and now number in the thousands. We propose a standard nomenclature and suggest the use of a centralized database for all cell line names and a minimum set of information for reporting new derivations. 相似文献
40.
Lazaro E Tram LT Bellecave P Guidicelli GL Anies G Thu HH Debelleix MP Vray M Recordon-Pinson P Taupin JL Lien TT Fleury H 《PloS one》2011,6(10):e26244