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51.
Kazuyo Maria Tasaki 《Progress in biophysics and molecular biology》2013,111(2-3):144-146
This paper discusses the concept of circular causality in “biological relativity” (Noble, Interface Focus. 2, 56-64, 2012) in the context of integrative and multi-scale systems approaches to biology. It also discusses the relationship between systems biology and traditional medicine (sometimes called scholarly medical traditions) mainly from East Asia and India. Systems biology helps illuminate circular processes identified in traditional medicine, while the systems concept of attractors in complex systems will also be important in analysing dynamic balance in the body processes that traditional medicine is concerned with. Ways of nudging disordered processes towards good attractors through the use of traditional medicines can lead to the development of new ways not only of curing disease but also of its prevention. Examples are given of cost-effective multi-component remedies that use integrative ideas derived from traditional medicine. 相似文献
52.
Ken'ichiro Matsumoto Yoshikazu Tanaka Tsuyoshi Watanabe Ren Motohashi Koji Ikeda Kota Tobitani Min Yao Isao Tanaka Seiichi Taguchi 《Applied and environmental microbiology》2013,79(19):6134-6139
NADPH-dependent acetoacetyl-coenzyme A (acetoacetyl-CoA) reductase (PhaB) is a key enzyme in the synthesis of poly(3-hydroxybutyrate) [P(3HB)], along with β-ketothiolase (PhaA) and polyhydroxyalkanoate synthase (PhaC). In this study, PhaB from Ralstonia eutropha was engineered by means of directed evolution consisting of an error-prone PCR-mediated mutagenesis and a P(3HB) accumulation-based in vivo screening system using Escherichia coli. From approximately 20,000 mutants, we obtained two mutant candidates bearing Gln47Leu (Q47L) and Thr173Ser (T173S) substitutions. The mutants exhibited kcat values that were 2.4-fold and 3.5-fold higher than that of the wild-type enzyme, respectively. In fact, the PhaB mutants did exhibit enhanced activity and P(3HB) accumulation when expressed in recombinant Corynebacterium glutamicum. Comparative three-dimensional structural analysis of wild-type PhaB and highly active PhaB mutants revealed that the beneficial mutations affected the flexibility around the active site, which in turn played an important role in substrate recognition. Furthermore, both the kinetic analysis and crystal structure data supported the conclusion that PhaB forms a ternary complex with NADPH and acetoacetyl-CoA. These results suggest that the mutations affected the interaction with substrates, resulting in the acquirement of enhanced activity. 相似文献
53.
Shuji Yonezawa Hidekuni Yamakawa Chie Muto Motoko Hosono Takahiko Yamamoto Kazunari Hattori Masahiro Sakagami Hiroko Togame Yoshikazu Tanaka Toru Nakano Hiroshi Takemoto Mitsuhiro Arisawa Satoshi Shuto 《Bioorganic & medicinal chemistry letters》2013,23(10):2912-2915
To improve the efficacy of the conformationally restricted BACE1 inhibitors, structural modifications were investigated using two strategies: (a) modification of the terminal aromatic ring and (b) insertion of a spacer between the aromatic rings. In the latter approach, another type of inhibitor 17 bearing an ethylene spacer between two aromatic rings was found to exhibit good BACE1 inhibitory activity, while the corresponding conformationally unrestricted compound 25 showed no activity. This result revealed an interesting effect of a conformational restriction with a cyclopropane ring. 相似文献
54.
Youichi Kawakita Masaki Seto Tomohiro Ohashi Toshiya Tamura Tadashi Yusa Hiroshi Miki Hidehisa Iwata Hidenori Kamiguchi Toshimasa Tanaka Satoshi Sogabe Yoshikazu Ohta Tomoyasu Ishikawa 《Bioorganic & medicinal chemistry》2013,21(8):2250-2261
A novel 7,6 fused bicyclic scaffold, pyrimido[4,5-b]azepine was designed to fit into the ATP binding site of the HER2/EGFR proteins. The synthesis of this scaffold was accomplished by an intramolecular Claisen-type condensation. As the results of optimization lead us to 4-anilino and 6-functional groups, we discovered 6-substituted amide derivative 19b, which has a 1-benzothiophen-4-yloxy group attached to the 4-anilino group. An X-ray co-crystal structure of 19b with EGFR demonstrated that the N-1 and N-3 nitrogens of the pyrimido[4,5-b]azepine scaffold make hydrogen-bonding interactions with the main chain NH of Met793 and the side chain of Thr854 via a water-mediated hydrogen bond network, respectively. In addition, the NH proton at the 9-position makes an additional hydrogen bond with the carbonyl group of Met793, as we expected. Compound 19b revealed potent HER2/EGFR kinase (IC50: 24/36 nM) and BT474 cell growth (GI50: 18 nM) inhibitory activities based on its pseudo-irreversible (PI) profile. 相似文献
55.
Yoshikazu Takagi Takane Fujimori Hajime Kaneko Kunio Kato 《Bioscience, biotechnology, and biochemistry》2013,77(11):2395-2396
Carcinogenesis is believed to be induced through the oxidative damage of DNA, and antioxidants are expected to suppress it. So, the polyphenolic antioxidants in daily foods were investigated to see whether they protect against genetic damage by active oxygen. In the evaluation, we used a bioassay and a chemical determination, a Salmonella mutagenicity test for mutation by a N-hydroxyl radical from one of the dietary carcinogens 3-amino-1-methyl-5H-pyrido[4,3-b]indole and the formation of 8-hydroxyl (8-OHdG) from 2′-deoxyguanosine (2′-dG) in a Fenton OH-radical generating system. Thirty-one antioxidants including flavonoids were compared in terms of radical-trapping activity with bacterial DNA and 2′-dG. Antioxidants inhibited the mutation but the IC50 values were in the mM order. Against 8-OHdG formation, only α-tocopherol had a suppressive effect with an IC50 of 1.5 μM. Thus, except α-tocopherol, the dietary antioxidants did not scavenge the biological radicals faster than bacterial DNA and intact 2′-dG, indicating that they failed to prevent oxidative gene damage and probably carcinogenesis. 相似文献
56.
Yoshikazu Izumi Kuninori Sato Yoshiki Tani Koichi Ogata 《Bioscience, biotechnology, and biochemistry》2013,77(11):2683-2684
Vitamin B6 is synthesized by green Cytisus scoparius callus and green Phellodendron amurense callus cultured on Linsmaier and Skoog Agar-medium with 10?5m of ±-naphthaleneacetic acid (NAA) and 10?6 m of 6-benzyladenine (BA). Even when thiamine and inositol were omitted from this medium, the growth and vitamin B6 content of Cytisus scoparius callus did not change. Vitamin B6 contents of clones of the calluses varied and were unstable during long-term subculture. Clonal selection was repeated to obtain stable strains with high vitamin B6 content, and the vitamin B6 content of one strain of green Cytisus scoparius callus became 4-times higher than that of the green leaves. 相似文献
57.
Yoshikazu Takagi Takane Fujimori Hajime Kaneko Kunio Kato 《Bioscience, biotechnology, and biochemistry》2013,77(3):787-788
The tetradecapeptide of a renin substrate, DRVYIHPFHLLVYS, was used as a substrate for assaying several fungal aspartic and acidic proteinases in the acidic pH range. Aspartic and acidic proteinases froll) Phycomycetes, Mucor and Rhizopus, and Deuteromycotina, Aspergillus and Penicillium, cleaved the tetradecapeptide at its tyrosyl4-isoleucyl5 (Y4-I5),histidyI6-proly7 (H6_P7) and leucyl11-valyl12 (L11-V12) bonds in the acidic pH range, while acidic proteinases type B and type A-I from Scytalidium lignicolumn, and those from Cladosporium and Basidiomycetes, Pycnoporus sanguineus, and the yeast, Rhodotorula glutinis; showed slightly different specificities towards the tetradecapeptide. Pepsin primarily cleaved the valy3-tyrosyl4 (V3-Y4) and leucyl10-leucyl11 (L10-L11) bonds. All of the aspartic and acidic proteinases of fungal origin tested in the present study have different specificities from that of pepsin. 相似文献
58.
59.
Yoshikazu Matsumura Toshihiro Nakanishi Masaru Iizuka Takehiko Yamamoto 《Bioscience, biotechnology, and biochemistry》2013,77(2):379-386
1. A trial test was attempted of complete hydrolysis of peptides and proteins into amino acids by enzymes. “Neutral proteinase” of Bacillus subtilis or “Alkalophilic proteinase” of a Streptomyces sp. was used for preliminary digestion of substrate, and a mixture of three aminopeptidases of Bacillus subtilis was employed for subsequent hydrolysis of proteinase digest.2. The oxidized insulin B chain was hydrolyzed completely by the method. Several proteins including enzymes which contained no or less cystine and cysteine were also hydrolyzed almost completely.3. On the other hand, certain glycoproteins were hydrolyzed to leave a few glycopeptides in which all glycomoieties of the proteins were retained. The implications of the results are discussed. 相似文献
60.
Yoshiki Tani Koichi Ogata Masao Ukita Tsuyoshi Nakamatsu Yoshikazu Izumi 《Bioscience, biotechnology, and biochemistry》2013,77(2):173-197
Escherichia freundii alkaline phosphatase was found in a membrane fraction and was purified by procedures involving spheroplast formation with lysozyme and EDTA, and DEAE-cellulose and Sephadex G-150 column chromatographies. Then this enzyme along with other phosphatases was investigated on the ability to transfer the phosphoryl group from p-nitrophenyl phosphate to pyridoxine. It was found that the ability of the transphosphorylation varied with these phosphatases. The transphosphorylation to hydroxy compounds such as alcohols, sugars and nucleosides was also compared. Escherichia freundii acid phosphatase showed the highest activity of transphosphorylation among phosphatases tested. The mechanism of transphosphorylation was discussed.An enzyme, pyridoxamine 5′-phosphate transaminase, was purified from the cell-free extract of Clostridium kainantoi. The purification procedures involved ammonium sulfate fractionation, protamine sulfate treatment and, DEAE-cellulose, hydroxylapatite, DEAE-Sephadex and Sephadex G-200 column chromatographies. The purified enzyme, which had approximately 2700-fold higher specific activity over the original extract, showed a single schlieren pattern in the ultracentrifuge. From the spectral analysis, it seemed that pyridoxamine 5′-phosphate transaminase did not contain pyridoxal 5′-phosphate as a prosthetic group. It was recognized that the transamination was accelerated by the addition of amino acid and was inhibited by diisopropyl phosphofluoride. Glutamic acid formed in the reaction was identified to be a D-isomer. A study on the substrate specificity showed that the enzyme might be possible to be specific for pyridoxamine 5′-phosphate.The extracellular formation of vitamin B6 was searched in marine and terrestrial microorganisms. Two bacterial strains were selected and were identified as Vibrio and Flavobacterium, respectively. Marine microorganisms showed the considerable formation of vitamin B6 and the presence of vitamin B6 in sea water was also recognized. The cultural and reaction conditions for vitamin B6 formation by these strains were investigated. Glycerol was commonly the most effective compound on vitamin B6 formation among the compounds tested. It was suggested that both bacteria did not have the control system on vitamin B6 biosynthesis by the amount of possible end products. 相似文献