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排序方式: 共有588条查询结果,搜索用时 31 毫秒
91.
Takashi Seino Shintaro Kawasaki Mariko Shimokawa Hiroki Tamagawa Kohta Toshimitsu Masayuki Fujii Yuki Ohta Mami Matano Kosaku Nanki Kenta Kawasaki Sirirat Takahashi Shinya Sugimoto Eisuke Iwasaki Junichi Takagi Takao Itoi Minoru Kitago Yuko Kitagawa Takanori Kanai Toshiro Sato 《Cell Stem Cell》2018,22(3):454-467.e6
92.
Nakakita S Sumiyoshi W Miyanishi N Hirabayashi J 《Biochemical and biophysical research communications》2007,362(3):639-645
Hydrazinolysis is a versatile method to liberate N-linked glycans from glycoproteins. However, the method is usually performed with anhydrous hydrazine, a highly toxic and explosive chemical used in rocket fuel. Thus despite the need to produce functionally important glyco-materials, hydrazinolysis is limited to small scale (e.g., 0.2-1 mL) reactions. In the present study, we report an alternative procedure for hydrazinolysis using hydrazine monohydrate in place of anhydrous hydrazine. The developed procedure was applied to both purified glycoproteins (Taka-amylase and transferrin) and hen egg yolk protein fraction with comparable yields to the traditional method using anhydrous hydrazine. The sialyl linkage of alpha2-6disialobiantennary oligosaccharides proved to be fully stable. The developed procedure facilitated the large-scale preparation of N-linked glycans. The new method should make a substantial contribution to both small- and large-scale production of functional glycans, including therapeutically relevant human-type glycans. 相似文献
93.
Tetsuya Yabutani Mami Tsujimoto Shunsuke Ohira Shiho Shimizu Hideo Nakano 《Bioscience, biotechnology, and biochemistry》2017,81(7):1456-1459
A Gram-positive bacterium Lentzea sp. 7887 hydroxylates a cyclosporine derivative FR901459 into AS1837812 (9-hydroxide), which is an important intermediate of candidate drugs that target the hepatitis C virus. We screened a UV-induced mutant, named M-1, which showed about 1.2-fold higher conversion yields, 2-fold higher substrate concentrations (3.69 mM), and 2.5-fold higher yield per unit volume than the wild-type strain. 相似文献
94.
Maki Fukami Erina Suzuki Yoko Izumi Tomohiro Torii Satoshi Narumi Maki Igarashi Mami Miyado Momori Katsumi Yasuko Fujisawa Kazuhiko Nakabayashi Kenichiro Hata Akihiro Umezawa Yoichi Matsubara Junji Yamauchi Tsutomu Ogata 《Journal of cellular and molecular medicine》2017,21(10):2623-2626
The human genome encodes ~750 G‐protein‐coupled receptors (GPCRs), including prokineticin receptor 2 (PROKR2) involved in the regulation of sexual maturation. Previously reported pathogenic gain‐of‐function mutations of GPCR genes invariably encoded aberrant receptors with excessive signal transduction activity. Although in vitro assays demonstrated that an artificially created inactive mutant of PROKR2 exerted paradoxical gain‐of‐function effects when co‐transfected with wild‐type proteins, such a phenomenon has not been observed in vivo. Here, we report a heterozygous frameshift mutation of PROKR2 identified in a 3.5‐year‐old girl with central precocious puberty. The mutant mRNA escaped nonsense‐mediated decay and generated a GPCR lacking two transmembrane domains and the carboxyl‐terminal tail. The mutant protein had no in vitro signal transduction activity; however, cells co‐expressing the mutant and wild‐type PROKR2 exhibited markedly exaggerated ligand‐induced Ca2+ responses. The results indicate that certain inactive PROKR2 mutants can cause early puberty by enhancing the functional property of coexisting wild‐type proteins. Considering the structural similarity among GPCRs, this paradoxical gain‐of‐function mechanism may underlie various human disorders. 相似文献
95.
Hidaka K Kimura T Ruben AJ Uemura T Kamiya M Kiso A Okamoto T Tsuchiya Y Hayashi Y Freire E Kiso Y 《Bioorganic & medicinal chemistry》2008,16(23):10049-10060
Plasmepsin (Plm) is a potential target for new antimalarial drugs, but most reported Plm inhibitors have relatively low antimalarial activities. We synthesized a series of dipeptide-type HIV protease inhibitors, which contain an allophenylnorstatine-dimethylthioproline scaffold to exhibit potent inhibitory activities against Plm II. Their activities against Plasmodium falciparum in the infected erythrocyte assay were largely different from those against the target enzyme. To improve the antimalarial activity of peptidomimetic Plm inhibitors, we attached substituents on a structure of the highly potent Plm inhibitor KNI-10006. Among the derivatives, we identified alkylamino compounds such as 44 (KNI-10283) and 47 (KNI-10538) with more than 15-fold enhanced antimalarial activity, to the sub-micromolar level, maintaining their potent Plm II inhibitory activity and low cytotoxicity. These results suggest that auxiliary substituents on a specific basic group contribute to deliver the inhibitors to the target Plm. 相似文献
96.
Complexes possessing a soft donor η6-arene and hard donor acetylacetonate ligand, [(η6-p-cymene)Ru(κ2-O,O-acac-μ-CH)]2[OTf]2 (1) (OTf = trifluoromethanesulfonate; acac = acetylacetonate) and {Ar′ = 3,5-(CF3)-C6H3}, were prepared and fully characterized. The lability of the μ-CH linkage for complex 1 and the THF ligand of 2 allow access to the unsaturated cation [(η6-p-cymene)Ru(κ2-O,O-acac)]+. The reaction of with KTp {Tp = hydridotris(pyrazolyl)borate} produces . The azide complex forms upon reaction of with N3Ar (Ar = p-tolyl), and reaction of with CHCl3 at 100 °C yields the chloride-bridged binuclear complex . The details of solid-state structures of [(η6-p-cymene)Ru(κ2-O,O-acac-μ-CH)]2[OTf]2 (1), and are disclosed. 相似文献
97.
98.
A diverse array of secondary metabolites in plants represents the process of coevolution between the plants and their natural enemies including herbivores and pathogens. For defense, plants produce many toxic compounds that harm other organisms. However, if the target of these compounds is a fundamental biological process then the producing plant may also be harmed. In such cases self-resistance strategies must coevolve with the biosynthetic pathway of toxic metabolites. In this review, we discuss the recent elucidation of the self-resistance mechanism of camptothecin (CPT)-producing plants. In this case the target protein of CPT, topoisomerase (Top) 1, has been mutated in order to overcome the toxicity of the compound. Similar mechanisms might also be used by other plants producing different toxic compounds which target fundamental metabolism. 相似文献
99.
100.
Tadanobu Takahashi Asako Hashimoto Mami Maruyama Makoto Kiso Yoshihiro Kawaoka Yasuo Suzuki Takashi Suzuki 《FEBS letters》2009,583(19):3171-3174
To identify a determinant of human H3 hemagglutinin (HA) amino acid residues linked to the recognition of molecular species of sialic acid, we generated six mutant viruses possessing either the wild-type HA gene from A/Memphis/1/71 (H3N2) or a genetically single-mutated HA gene at position 137, 144, 155, 158 or 193 from a genetic backbone of A/WSN/33 (H1N1) by reverse genetics. We evaluated the binding ability with four types of synthetic sialylglycolipids. The results indicate that the amino acid substitutions Thr155 to Tyr and Glu158 to Gly in H3 HA facilitate virus binding to N-glycolylneuraminic acid. 相似文献