全文获取类型
收费全文 | 1280篇 |
免费 | 55篇 |
出版年
2023年 | 2篇 |
2021年 | 11篇 |
2020年 | 8篇 |
2019年 | 13篇 |
2018年 | 12篇 |
2017年 | 19篇 |
2016年 | 26篇 |
2015年 | 46篇 |
2014年 | 64篇 |
2013年 | 64篇 |
2012年 | 73篇 |
2011年 | 86篇 |
2010年 | 60篇 |
2009年 | 51篇 |
2008年 | 73篇 |
2007年 | 78篇 |
2006年 | 71篇 |
2005年 | 99篇 |
2004年 | 86篇 |
2003年 | 76篇 |
2002年 | 61篇 |
2001年 | 13篇 |
2000年 | 11篇 |
1999年 | 19篇 |
1998年 | 12篇 |
1997年 | 24篇 |
1996年 | 11篇 |
1995年 | 17篇 |
1994年 | 13篇 |
1993年 | 12篇 |
1992年 | 8篇 |
1991年 | 11篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 9篇 |
1987年 | 9篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1978年 | 9篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1975年 | 7篇 |
1973年 | 3篇 |
1971年 | 2篇 |
1961年 | 1篇 |
排序方式: 共有1335条查询结果,搜索用时 388 毫秒
91.
Tomohiro Kimura Ryutaro Shirakawa Nobuhiro Yaoita Takashi Hayashi Keisuke Nagano Hisanori Horiuchi 《FEBS letters》2014
Quinoline derivatives such as chloroquine and primaquine are widely used for the treatment of malaria. These drugs are also used for the treatment of trypanosomiasis, and more recently for cancer therapy. However, molecular target(s) of these drugs remain unclear. In this study, we have identified human pyridoxal kinase as a binding protein of primaquine. Primaquine inhibited pyridoxal kinases of malaria, trypanosome and human, while chloroquine inhibited only malaria pyridoxal kinase. Thus, we have identified pyridoxal kinase as a possible target molecule of the antimalarial drugs chloroquine and primaquine. 相似文献
92.
Kazuo Hara Nobuhiro ShojimaJun Hosoe Takashi Kadowaki 《Biochemical and biophysical research communications》2014
Genome-wide association studies (GWAS) have identified over 70 loci associated with type 2 diabetes (T2D). Most genetic variants associated with T2D are common variants with modest effects on T2D and are shared with major ancestry groups. To what extent the genetic component of T2D can be explained by common variants relies upon the shape of the genetic architecture of T2D. Fine mapping utilizing populations with different patterns of linkage disequilibrium and functional annotation derived from experiments in relevant tissues are mandatory to track down causal variants responsible for the pathogenesis of T2D. 相似文献
93.
94.
Tsuneomi Kawasaki Mai Nakaoda Nobuhiro Kaito Taisuke Sasagawa Kenso Soai 《Origins of life and evolution of the biosphere》2010,40(1):65-78
The achiral hydrocarbon tetraphenylethylene crystallizes in enantiomorphous forms (chiral space group: P21) to afford right- and left-handed hemihedral crystals, which can be recognized by solid-state circular dichroism spectroscopic
analysis. Chiral organic crystals of tetraphenylethylene mediated enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde
to give, in conjunction with asymmetric autocatalysis with amplification of chirality, almost enantiomerically pure (S)- and (R)-5-pyrimidyl alkanols whose absolute configurations were controlled efficiently by the crystalline chirality of the tetraphenylethylene
substrate. Tetrakis(p-chlorophenyl)ethylene and tetrakis(p-bromophenyl)ethylene also show chirality in the crystalline state, which can also act as a chiral substrate and induce enantioselectivity
of diisopropylzinc addition to pyrimidine-5-carbaldehyde in asymmetric autocatalysis to give enantiomerically enriched 5-pyrimidyl
alkanols with the absolute configuration correlated with that of the chiral crystals. Highly enantioselective synthesis has
been achieved using chiral crystals composed of achiral hydrocarbons, tetraphenylethylenes, as chiral inducers. This chemical
system enables significant amplification of the amount of chirality using spontaneously formed chiral crystals of achiral
organic compounds as the seed for the chirality of asymmetric autocatalysis. 相似文献
95.
Nobuhiro Sasai Mitsuyoshi Nakao Pierre-Antoine Defossez 《Nucleic acids research》2010,38(15):5015-5022
DNA methylation is an essential epigenetic mark. Three classes of mammalian proteins recognize methylated DNA: MBD proteins, SRA proteins and the zinc-finger proteins Kaiso, ZBTB4 and ZBTB38. The last three proteins can bind either methylated DNA or unmethylated consensus sequences; how this is achieved is largely unclear. Here, we report that the human zinc-finger proteins Kaiso, ZBTB4 and ZBTB38 can bind methylated DNA in a sequence-specific manner, and that they may use a mode of binding common to other zinc-finger proteins. This suggests that many other sequence-specific methyl binding proteins may exist. 相似文献
96.
Zhang D Kato Y Zhang L Fujimoto M Tsutsumi N Sodmergen Sakamoto W 《The Plant cell》2010,22(11):3710-3725
FtsH is an ATP-dependent metalloprotease present as a hexameric heterocomplex in thylakoid membranes. Encoded in the Arabidopsis thaliana YELLOW VARIEGATED2 (VAR2) locus, FtsH2 is one isoform among major Type A (FtsH1/5) and Type B (FtsH2/8) isomers. Mutants lacking FtsH2 (var2) and FtsH5 (var1) are characterized by a typical leaf-variegated phenotype. The functional importance of the catalytic center (comprised by the zinc binding domain) in FtsH2 was assessed in this study by generating transgenic plants that ectopically expressed FtsH2(488), a proteolytically inactive version of FtsH2. The resulting amino acid substitution inhibited FtsH protease activity in vivo when introduced into Escherichia coli FtsH. By contrast, expression of FtsH2(488) rescued not only leaf variegation in var2 but also seedling lethality in var2 ftsh8, suggesting that the protease activity of Type B isomers is completely dispensable, which implies that the chloroplastic FtsH complex has protease sites in excess and that they act redundantly rather than coordinately. However, expression of FtsH2(488) did not fully rescue leaf variegation in var1 var2 because the overall FtsH levels were reduced under this background. Applying an inducible promoter to our complementation analysis revealed that rescue of leaf variegation indeed depends on the overall amount of FtsH. Our results elucidate protein activity and its amount as important factors for the function of FtsH heterocomplexes that are composed of multiple isoforms in the thylakoid membrane. 相似文献
97.
Nobuhiro Hayashi Masami Takeuchi Teruyuki Nakanishi Keiichiro Hashimoto Johannes Martinus Dijkstra 《Fish & shellfish immunology》2010,28(1):72-76
The cytoplasmic tail of mammalian CD8α binds the kinase LCK in a zinc-dependent manner. In analogy with a previous study for humans (Kim et al., 2003) peptides were synthesized from rainbow trout CD8α and LCK. Surface plasmon resonance (SPR) analysis indicated that also in fish these molecules bind to each other in a zinc-dependent manner. 相似文献
98.
Nobuhiro Mifune Hirofumi Hashimoto Toshio Yamagishi 《Evolution and human behavior》2010,31(2):109-117
To test the hypothesis that sensitivity to monitoring drives people to act altruistically toward members of their own community, two experiments investigated whether an eye-like painting promotes altruism toward in-group members, but not toward out-group members. Participants played the role of dictator in a dictator game with another participant (a recipient) who was from the minimal in-group or out-group. Participants knew whether their recipient was an in-group member or an out-group member, but were informed that their recipient did not know the group membership of the dictator. In-group favoritism occurred only when participants were facing a computer desktop which displayed a painting of eyes, but did not occur in the absence of eyes. These findings demonstrate that the eye painting displayed on the participant's computer screen worked as a cue for monitoring and thus enhanced the participant's altruistic behavior. 相似文献
99.
Viivi Majava Chaozhan Wang Matti Myllykoski Salla M. Kangas Sung Ung Kang Nobuhiro Hayashi Peter Baumgärtel Anthony M. Heape Gert Lubec Petri Kursula 《Amino acids》2010,39(1):59-71
Myelin basic protein (MBP) is present between the cytoplasmic leaflets of the compact myelin membrane in both the peripheral and central nervous systems, and characterized to be intrinsically disordered in solution. One of the best-characterized protein ligands for MBP is calmodulin (CaM), a highly acidic calcium sensor. We pulled down MBP from human brain white matter as the major calcium-dependent CaM-binding protein. We then used full-length brain MBP, and a peptide from rodent MBP, to structurally characterize the MBP–CaM complex in solution by small-angle X-ray scattering, NMR spectroscopy, synchrotron radiation circular dichroism spectroscopy, and size exclusion chromatography. We determined 3D structures for the full-length protein–protein complex at different stoichiometries and detect ligand-induced folding of MBP. We also obtained thermodynamic data for the two CaM-binding sites of MBP, indicating that CaM does not collapse upon binding to MBP, and show that CaM and MBP colocalize in myelin sheaths. In addition, we analyzed the post-translational modifications of rat brain MBP, identifying a novel MBP modification, glucosylation. Our results provide a detailed picture of the MBP–CaM interaction, including a 3D model of the complex between full-length proteins. 相似文献
100.
Yasushi Todoroki Kumi Naiki Hikaru Aoyama Minaho Shirakura Kotomi Ueno Masaharu Mizutani Nobuhiro Hirai 《Bioorganic & medicinal chemistry letters》2010,20(18):5506-5509
The plant growth-retardant uniconazole (UNI), a triazole inhibitor of gibberellin biosynthetic enzyme (CYP701A), inhibits multiple P450 enzymes including ABA 8′-hydroxylase (CYP707A), a key enzyme in ABA catabolism. Azole P450 inhibitors bind to a P450 active site by both coordinating to the heme-iron atom via sp2 nitrogen and interacting with surrounding protein residues through a lipophilic region. We hypothesized that poor selectivity of UNI may result from adopting a distinct conformation and orientation for different active sites. Based on this hypothesis, we designed and synthesized novel UNI analogs with a disubstituted azole ring (DSI). These analogs were expected to have higher selectivity than UNI because the added functional group may interact with the active site to restrict orientation of the molecule in the active site. DSI-505ME and DSI-505MZ, which have an imidazolyl group with a methyl 5-acrylate, strongly inhibited recombinant CYP707A3, with no growth-retardant effect. 相似文献