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121.
Shigemitsu Matsumoto Naoki Miyamoto Takaharu Hirayama Hideyuki Oki Kengo Okada Michiko Tawada Hidehisa Iwata Kazuhide Nakamura Seiji Yamasaki Hiroshi Miki Akira Hori Shinichi Imamura 《Bioorganic & medicinal chemistry》2013,21(24):7686-7698
To identify compounds with potent antitumor efficacy for various human cancers, we aimed to synthesize compounds that could inhibit c-mesenchymal epithelial transition factor (c-Met) and vascular endothelial growth factor receptor 2 (VEGFR2) kinases. We designed para-substituted inhibitors by using co-crystal structural information from c-Met and VEGFR2 in complex with known inhibitors. This led to the identification of compounds 3a and 3b, which were capable of suppressing both c-Met and VEGFR2 kinase activities. Further optimization resulted in pyrazolone and pyridone derivatives, which could form intramolecular hydrogen bonds to enforce a rigid conformation, thereby producing potent inhibition. One compound of particular note was the imidazo[1,2-a]pyridine derivative (26) bearing a 6-methylpyridone ring, which strongly inhibited both c-Met and VEGFR2 enzyme activities (IC50 = 1.9, 2.2 nM), as well as proliferation of c-Met-addicted MKN45 cells and VEGF-stimulated human umbilical vein endothelial cells (IC50 = 5.0, 1.8 nM). Compound 26 exhibited dose-dependent antitumor efficacy in vivo in MKN45 (treated/control ratio [T/C] = 4%, po, 5 mg/kg, once-daily) and COLO205 (T/C = 13%, po, 15 mg/kg, once-daily) mouse xenograft models. 相似文献
122.
Lidiya Stavitskaya Michael J. Seminerio Jason R. Healy Bahar Noorbakhsh Rae R. Matsumoto Andrew Coop 《Bioorganic & medicinal chemistry》2013,21(17):4923-4927
A series of ring-constrained phenylpropyloxyethylamines, partial opioid structure analogs and derivatives of a previously studied sigma (σ) receptor ligand, was synthesized and evaluated at σ and opioid receptors for receptor selectivity. The results of this study identified several compounds with nanomolar affinity at both σ receptor subtypes. Compounds 6 and 9 had the highest selectivity for both σ receptor subtypes, compared to μ opioid receptors. In addition, compounds 6 and 9 significantly reduced the convulsive effects of cocaine in mice, which would be consistent with antagonism of σ receptors. 相似文献
123.
Atsuko Kushi Takashi Matsumoto Daisuke Yoshida 《Bioscience, biotechnology, and biochemistry》2013,77(9):1979-1982
A mutagenic fraction was separated by gas chromatography (gc) from the gaseous phase of protein pyrolyzate and a compound in the fraction was identified as hydrogen cyanide (hcn). Authentic hcn shows mutagenicity. It is proposed that most of the mutagenic activity in the gaseous phase of protein pyrolyzate is due to hcn. 相似文献
124.
Masao Fujimaki Makoto Tajima Teruyo Matsumoto 《Bioscience, biotechnology, and biochemistry》2013,77(10):1228-1231
The free amino acids of potatoes irradiated with the doses of 7,000, 15,000 and 30,000 rad were determined by ion-exchange chromatography.After 15 days storage following irradiation, it was shown that the concentration of asparatic acid, proline and aliphatic amino acids increased with increasing irradiation doses, while that of basic amino acids and glutamic acid especially decreased. However, after 105 days of storage, the similarity of the free amino acid content of irradiated potatoes to that of non-irradiated and non-stored potatoes was observed.On the concentration of protein-bound amino acids, there were no significant differences between non-irradiated and 15,000 rad irradiated potatoes. 相似文献
125.
Daisuke Yoshida Hiroshi Nishigata Takashi Matsumoto 《Bioscience, biotechnology, and biochemistry》2013,77(8):1769-1770
An extracellular exo-maltohexaohydrolase [EC 3.2.1.98] from a Klebsiella pneumoniae (Aerobacter aerogenes) mutant produced about 40% maltohexaose (G6) from short-chain amylose ( =23). Mostly G6 was produced from maltooligosaccharides larger than G6 by an exo-mechanism action. It also hydrolyzed G6 and shorter maltooligosaccharides to give smaller maltooligosaccharides. Its position specificity of action on G3 through G8 was studied with maltodextrins specifically labeled at the reducing-end glucose unit with 14C. The highest frequency of cleavage was at the second bond from the reducing end in G3 through G6. For G7 and G8, the sixth bond from the nonreducing end of the substrate was cleaved with absolute specificity by the exo-mechanism action.Kinetic parameters of the exo-maltohexaohydrolase on various substrates were also studied. The Michaelis constant (Km) for short-chain amylose was the smallest among the various substrates examined.G6 was also formed from G4 by a transfer action of the enzyme, with an action pattern dependent on the substrate concentration. 相似文献
126.
127.
Tsutomu Yoshida Shoko Shinoda Tsuneya Matsumoto Satoru Watarai 《Bioscience, biotechnology, and biochemistry》2013,77(12):3093-3095
A strain of Alcaligenes isolated from soil was a good producer of β-glucuronidase, and the enzyme was purified from the cell-free extract by sequential column chromatography on DEAE-Toyopearl, Toyopearl HW-55F, and Phenyl-Sepharose CL-4B. By these procedures, two β-glucuronidases designated as β-glucuronidases I and II were purified 240- and 508-fold, respectively. β-Glucuronidase I, with a molecular weight of 75,000, had an optimum pH at 7.5 and the enzyme II, with a molecular weight of 300,000, had maximum activity at pH 6.0. Both enzymes were strongly inhibited by saccharo-1,4-lactone, glucaro-δ-lactam, p-chloromercuribenzoate, Hg2+, and N-bromosuccinimide. β-Glucuronidase I was active toward estrogen-3-β-glucuronides and inert toward β-glucuronide conjugates of menthol, estrogen-17β-, estrogen-16α-, androsterone-3α-, testosterone-17β-, cortisol-17α-. β-Glucuronidase II hydrolyzed all of these substrates. β-Glucuronidase I was inhibited by phenolphthalein and its glucuronide. 相似文献
128.
129.
Silvia Yuko Eguchi Naomichi Nishio Shiro Nagai 《Bioscience, biotechnology, and biochemistry》2013,77(12):2941-2943
Resting cells of the methanogen strain HU, a formate-utilizing methanogenic bacterium, was able to utilize formate or hydrogen as electron donor for the production of NADPH from NADP+ under suitable conditions. In the presence of 0.2% Triton X-100 and 0.3 m potassium phosphate, pH 9.0 at 30°C, the resting cells could convert ca. 60% of the exogenous NADP+ into NADPH yielding ca. 6 g NADPH/liter. Phosphate ions greatly enhanced the NADPH production. 相似文献
130.
Shohei Sakuda Akira Isogai Tsukasa Makita Shogo Matsumoto Koshi Koseki Hisashi Kodama 《Bioscience, biotechnology, and biochemistry》2013,77(12):3251-3259
The structures of allosamidin (1) and methylallosamidin (2), novel insect chitinase inhibitors, were elucidated as 1 and 2 by acid hydrolysis experiments and analyses of 2d-NMR spectra. They are unique basic pseudotrisaccharides consisting of 2-acetamido-2-deoxy-d-allose (N-acetyl-d- allosamine) and a novel aminocyclitol derivative (3), termed allosamizoline. 相似文献