全文获取类型
收费全文 | 2020篇 |
免费 | 156篇 |
出版年
2024年 | 3篇 |
2023年 | 7篇 |
2022年 | 22篇 |
2021年 | 36篇 |
2020年 | 25篇 |
2019年 | 37篇 |
2018年 | 38篇 |
2017年 | 38篇 |
2016年 | 66篇 |
2015年 | 96篇 |
2014年 | 94篇 |
2013年 | 148篇 |
2012年 | 158篇 |
2011年 | 162篇 |
2010年 | 96篇 |
2009年 | 84篇 |
2008年 | 120篇 |
2007年 | 134篇 |
2006年 | 125篇 |
2005年 | 118篇 |
2004年 | 105篇 |
2003年 | 111篇 |
2002年 | 101篇 |
2001年 | 16篇 |
2000年 | 22篇 |
1999年 | 21篇 |
1998年 | 20篇 |
1997年 | 14篇 |
1996年 | 17篇 |
1995年 | 11篇 |
1994年 | 13篇 |
1993年 | 15篇 |
1992年 | 11篇 |
1991年 | 14篇 |
1990年 | 3篇 |
1989年 | 6篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 8篇 |
1982年 | 6篇 |
1981年 | 8篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 7篇 |
1975年 | 3篇 |
1972年 | 2篇 |
1971年 | 3篇 |
排序方式: 共有2176条查询结果,搜索用时 15 毫秒
991.
Alexandra I. Sorochkina Sergei I. Kovalchuk Elena O. Omarova Alexander A. Sobko Еlena А. Kotova Yuri N. Antonenko 《生物化学与生物物理学报:生物膜》2013
Introducing a charged group near the N-terminus of gramicidin A (gA) is supposed to suppress its ability to form ion channels by restricting its head-to-head dimerization. The present study dealt with the activity of [Lys1]gA, [Lys3]gA, [Glu1]gA, [Glu3]gA, [Lys2]gA, and [Lys5]gA in model membrane systems (planar lipid bilayers and liposomes) and erythrocytes. In contrast to the Glu-substituted peptides, the lysine derivatives of gA caused non-specific liposomal leakage monitored by fluorescence dequenching of lipid vesicles loaded with carboxyfluorescein or other fluorescent dyes. Measurements of electrical current through a planar lipid membrane revealed formation of giant pores by Lys-substituted analogs, which depended on the presence of solvent in the bilayer lipid membrane. The efficacy of unselective pore formation in liposomes depended on the position of the lysine residue in the amino acid sequence, increasing in the row: [Lys2]gA < [Lys5]gA < [Lys1]gA < [Lys3]gA. The similar series of potency was exhibited by the Lys-substituted gA analogs in facilitating erythrocyte hemolysis, whereas the Glu-substituted analogs showed negligible hemolytic activity. Oligomerization of the Lys-substituted peptides is suggested to be involved in the process of nonselective pore formation. 相似文献
992.
993.
Tatyana I. Rokitskaya Tatyana M. Ilyasova Inna I. Severina Yuri N. Antonenko Vladimir P. Skulachev 《European biophysics journal : EBJ》2013,42(6):477-485
Protonophores can be considered as candidates for anti-obesity drugs and tools to prevent excessive reactive oxygen species production in mitochondria by means of a limited decrease in the mitochondrial potential. Experimentally used protonophores are weak acids that can carry protons across a membrane in a neutral (protonated) form, and they come back in an anionic (deprotonated) form. A cationic derivative of rhodamine 19 and plastoquinone (SkQR1) was recently shown to possess uncoupling activity in mitochondria and in intact cells. In this article, we studied the mechanism of action of SkQR1 and its plastoquinone-lacking analog (C12R1) on a planar bilayer lipid membrane by applying voltage jumps. The steady-state current was proportional to the C12R1 concentration in a manner as if the monomeric form of the carrier were operative. As predicted by the carrier model, at high pH, when rhodamines were mainly deprotonated, the current changed immediately following a jump in the applied potential and then remained constant. By contrast, at low pH, the current relaxed from an initially high value to a lower value since the protonated carrier cations were redistributed in the membrane. An inverse pH dependence was revealed with the anionic protonophore CCCP. The dependence of the SkQR1 protonophorous activity on voltage exhibited an increase at high voltages, an effect that might facilitate mild (self-limited) uncoupling of mitochondria. 相似文献
994.
Daria V. Ilatovskaya Vladislav Chubinskiy-Nadezhdin Tengis S. Pavlov Leonid S. Shuyskiy Viktor Tomilin Oleg Palygin Alexander Staruschenko Yuri A. Negulyaev 《Cell and tissue research》2013,354(3):783-792
Dynamic remodeling of the actin cytoskeleton plays an essential role in cell migration and various signaling processes in living cells. One of the critical factors that controls the nucleation of new actin filaments in eukaryotic cells is the actin-related protein 2/3 (Arp2/3) complex. Recently, two novel classes of small molecules that bind to different sites on the Arp2/3 complex and inhibit its ability to nucleate F-actin have been discovered and described. The current study aims at investigating the effects of CK-0944666 (CK-666) and its analogs (CK-869 and inactive CK-689) on the reorganization of the actin microfilaments in the cortical collecting duct cell line, M-1. We show that treatment with CK-666 and CK869 results in the reorganization of F-actin and drastically affects cell motility rate. The concentrations of the compounds used in this study (100–200 μM) neither cause loss of cell viability nor influence cell shape or monolayer integrity; hence, the effects of described compounds were not due to structural side effects. Therefore, we conclude that the Arp2/3 complex plays an important role in cell motility and F-actin reorganization in M-1 cells. Furthermore, CK-666 and its analogs are useful tools for the investigation of the Arp2/3 complex. 相似文献
995.
Junichi M. Imoto Kenji Saitoh Takeshi Sasaki Takahiro Yonezawa Jun Adachi Yuri P. Kartavtsev Masaki Miya Mutsumi Nishida Naoto Hanzawa 《Gene》2013
The distribution of freshwater taxa is a good biogeographic model to study pattern and process of vicariance and dispersal. The subfamily Leuciscinae (Cyprinidae, Teleostei) consists of many species distributed widely in Eurasia and North America. Leuciscinae have been divided into two phyletic groups, leuciscin and phoxinin. The phylogenetic relationships between major clades within the subfamily are poorly understood, largely because of the overwhelming diversity of the group. The origin of the Far Eastern phoxinin is an interesting question regarding the evolutionary history of Leuciscinae. Here we present phylogenetic analysis of 31 species of Leuciscinae and outgroups based on complete mitochondrial genome sequences to clarify the phylogenetic relationships and to infer the evolutionary history of the subfamily. 相似文献
996.
997.
998.
Yuri Nishimura Hiroki Shudo Hirokazu Seto Yu Hoshino Yoshiko Miura 《Bioorganic & medicinal chemistry letters》2013,23(23):6390-6395
The glycopolymers for glycosaminoglycan mimic were synthesized, and the inhibitory effects of Alzheimer’s β-secretase (BACE-1) were examined. The regio-selective sulfation was conducted on N-acetyl glucosamine (GlcNAc), and the acrylamide derivatives were synthesized with the consequent sulfated GlcNAc. The glycopolymers were synthesized with acrylamide using radical initiator. The glycopolymer with sulfated GlcNAc showed the strong inhibitory effect on BACE-1, and the inhibitory effects were dependent on the sulfation positions. Especially, glycopolymers carrying 3,4,6-O-sulfo-GlcNAc showed the strong inhibitory effect. The docking simulation suggested that glycopolymers bind to the active site of BACE-1. 相似文献
999.
Grigory Veinberg Maxim Vorona Liga Zvejniece Reinis Vilskersts Edijs Vavers Edvards Liepinsh Helena Kazoka Sergey Belyakov Anatoly Mishnev Jevgenijs Kuznecovs Sergejs Vikainis Natalja Orlova Anton Lebedev Yuri Ponomaryov Maija Dambrova 《Bioorganic & medicinal chemistry》2013,21(10):2764-2771
Novel positive allosteric modulators of sigma-1 receptor represented by 2-(5-methyl-4-phenyl-2-oxopyrrolidin-1-yl)-acetamide enantiomers were synthesised using an asymmetric Michael addition of 2-nitroprop-1-enylbenzene to diethyl malonate. Following the chromatographic separation of the methyl erythro- and threo-4-nitro-3R- and 3S-phenylpentanoate diastereoisomers, target compounds were obtained by their reductive cyclisation into 5-methyl-4-phenylpyrrolidin-2-one enantiomers and the attachment of the acetamide group to the heterocyclic nitrogen. Experiments with electrically stimulated rat vas deference contractions induced by the PRE-084, an agonist of sigma-1 receptor, showed that (4R,5S)- and (4R,5R)-2-(5-methyl-4-phenyl-2-oxopyrrolidin-1-yl)-acetamides with an R-configuration at the C-4 chiral centre in the 2-pyrrolidone ring were more effective positive allosteric modulators of sigma-1 receptor than were their optical antipodes. 相似文献
1000.
Sho Konno Pillaiyar Thanigaimalai Takehito Yamamoto Kiyohiko Nakada Rie Kakiuchi Kentaro Takayama Yuri Yamazaki Fumika Yakushiji Kenichi Akaji Yoshiaki Kiso Yuko Kawasaki Shen-En Chen Ernesto Freire Yoshio Hayashi 《Bioorganic & medicinal chemistry》2013,21(2):412-424
We describe here the design, synthesis and biological evaluation of a series of molecules toward the development of novel peptidomimetic inhibitors of SARS-CoV 3CLpro. A docking study involving binding between the initial lead compound 1 and the SARS-CoV 3CLpro motivated the replacement of a thiazole with a benzothiazole unit as a warhead moiety at the P1′ site. This modification led to the identification of more potent derivatives, including 2i, 2k, 2m, 2o, and 2p, with IC50 or Ki values in the submicromolar to nanomolar range. In particular, compounds 2i and 2p exhibited the most potent inhibitory activities, with Ki values of 4.1 and 3.1 nM, respectively. The peptidomimetic compounds identified through this process are attractive leads for the development of potential therapeutic agents against SARS. The structural requirements of the peptidomimetics with potent inhibitory activities against SARS-CoV 3CLpro may be summarized as follows: (i) the presence of a benzothiazole warhead at the S1′-position; (ii) hydrogen bonding capabilities at the cyclic lactam of the S1-site; (iii) appropriate stereochemistry and hydrophobic moiety size at the S2-site and (iv) a unique folding conformation assumed by the phenoxyacetyl moiety at the S4-site. 相似文献