全文获取类型
收费全文 | 1293篇 |
免费 | 87篇 |
出版年
2022年 | 10篇 |
2021年 | 16篇 |
2020年 | 6篇 |
2019年 | 17篇 |
2018年 | 19篇 |
2017年 | 15篇 |
2016年 | 25篇 |
2015年 | 35篇 |
2014年 | 43篇 |
2013年 | 70篇 |
2012年 | 77篇 |
2011年 | 80篇 |
2010年 | 44篇 |
2009年 | 35篇 |
2008年 | 55篇 |
2007年 | 67篇 |
2006年 | 61篇 |
2005年 | 48篇 |
2004年 | 63篇 |
2003年 | 45篇 |
2002年 | 47篇 |
2001年 | 39篇 |
2000年 | 43篇 |
1999年 | 44篇 |
1998年 | 12篇 |
1997年 | 16篇 |
1996年 | 7篇 |
1995年 | 20篇 |
1994年 | 12篇 |
1993年 | 11篇 |
1992年 | 25篇 |
1991年 | 24篇 |
1990年 | 25篇 |
1989年 | 29篇 |
1988年 | 33篇 |
1987年 | 21篇 |
1986年 | 22篇 |
1985年 | 17篇 |
1984年 | 18篇 |
1983年 | 6篇 |
1982年 | 16篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 5篇 |
1973年 | 4篇 |
1970年 | 5篇 |
1969年 | 5篇 |
排序方式: 共有1380条查询结果,搜索用时 15 毫秒
71.
Naoto Burioka Miyako Takata Masahiro Endo Masanori Miyata Kenichi Takeda Hiroki Chikumi 《Chronobiology international》2013,30(1):183-189
This study examined whether in vivo exposure to a β2‐adrenoceptor agonist, tulobuterol, induces human Period1 (hPer1) mRNA expression in cells from peripheral whole blood. In one experiment, oral tulobuterol was administered to five healthy volunteers at 22:00 h, while in another, a transdermally tulobuterol patch was applied to the same five subjects at 20:00 h. In each experiment, serum tulobuterol concentrations were measured at four time points, and total RNA was isolated from peripheral blood cells for determinations of hPer1 mRNA expression by real‐time polymerase chain reaction. Both the tulobuterol tablet and the transdermal patch increased hPer1 mRNA expression, suggesting that analyses of human peripheral blood cells could reliably represent peripheral clock gene mRNA expression in vivo. 相似文献
72.
Koichi Eguchi Yasuhide Yoshioka Hideki Yoshida Kazushige Morishita Seiji Miyata Hiroshi Hiai Masamitsu Yamaguchi 《Experimental cell research》2013
The Drosophila sponge (spg)/CG31048 gene belongs to the dedicator of cytokinesis (DOCK) family genes that are conserved in a wide variety of species. DOCK family members are known as DOCK1–DOCK11 in mammals. Although DOCK1 and DOCK2 involve neurite elongation and immunocyte differentiation, respectively, the functions of other DOCK family members are not fully understood. Spg is a Drosophila homolog of mammalian DOCK3 and DOCK4. Specific knockdown of spg by the GMR-GAL4 driver in eye imaginal discs induced abnormal eye morphology in adults. To mark the photoreceptor cells in eye imaginal discs, we used a set of enhancer trap strains that express lacZ in various sets of photoreceptor cells. Immunostaining with anti-Spg antibodies and anti-lacZ antibodies revealed that Spg is localized mainly in R7 photoreceptor cells. Knockdown of spg by the GMR-GAL4 driver reduced signals of R7 photoreceptor cells, suggesting involvement of Spg in R7 cell differentiation. Furthermore, immunostaining with anti-dpERK antibodies showed the level of activated ERK signal was reduced extensively by knockdown of spg in eye discs, and both the defects in eye morphology and dpERK signals were rescued by over-expression of the Drosophila raf gene, a component of the ERK signaling pathway. Furthermore, the Duolink in situ Proximity Ligation Assay method detected interaction signals between Spg and Rap1 in and around the plasma membrane of the eye disc cells. Together, these results indicate Spg positively regulates the ERK pathway that is required for R7 photoreceptor cell differentiation and the regulation is mediated by interaction with Rap1 during development of the compound eye. 相似文献
73.
74.
Keishi Shimokawa Yoshinori Ueda Zenzaburo Kasai 《Bioscience, biotechnology, and biochemistry》2013,77(11):2021-2024
ABSTRACTJapanese apricot, Prunus mume Sieb. et Zucc., biosynthesizes the l-phenylalanine-derived cyanogenic glucosides prunasin and amygdalin. Prunasin has biological properties such as anti-inflammation, but plant extraction and chemical synthesis are impractical. In this study, we identified and characterized UGT85A47 from Japanese apricot. Further, UGT85A47 was utilized for prunasin microbial production. Full-length cDNA encoding UGT85A47 was isolated from Japanese apricot after 5?- and 3?-RACE. Recombinant UGT85A47 stoichiometrically catalyzed UDP-glucose consumption and synthesis of prunasin and UDP from mandelonitrile. Escherichia coli C41(DE3) cells expressing UGT85A47 produced prunasin (0.64 g/L) from racemic mandelonitrile and glucose. In addition, co-expression of genes encoding UDP-glucose biosynthetic enzymes (phosphoglucomutase and UTP-glucose 1-phosphate uridiltransferase) and polyphosphate kinase clearly improved prunasin production up to 2.3 g/L. These results showed that our whole-cell biocatalytic system is significantly more efficient than the existing prunasin production systems, such as chemical synthesis. 相似文献
75.
To search precursors of ethylene in banana fruits, ethylene formation from acetate-2-14C and fumarate-2,3-14C by banana slices was studied. Ethylene-14C formation from acetate-2-l4C was reduced by the addition of malonate or β-hydroxypropionate, and it was enhanced in a sealed chamber in comparison with the case in an aeration chamber. No label of fumarate-2,3-14C was incorporated into ethylene.From these facts it was suggested that acetate-2-14C was incorporated into ethylene via malonate and β-hydroxypropionate. Participation of fumarate in ethylene biosynthesis of banana fruits was ruled out. β-Hydroxypropionate was postulated as an effective precursor of ethylene formation from acetate-2-l4C. 相似文献
76.
Kouichi Miyata Katsumi Tomoda Masao Isono 《Bioscience, biotechnology, and biochemistry》2013,77(10):1457-1462
The substrate specificity of Serratia protease was determined using various synthetic substrates. The enzyme did not participate in the hydrolysis of di- and tri-peptides except benzoylglycylleucinamide which was split at a limited rate into hippuric acid and leucinamide. The enzyme action on larger peptides was also studied. The enzyme cleaved the gly-leu bond in eledoisin related peptide and the gly-phe bond in bradykinin. The enzyme split oxidized insulin B-chain at twelve different peptide bonds. 相似文献
77.
Kouichi Miyata Katsumi Tomoda Masao Isono 《Bioscience, biotechnology, and biochemistry》2013,77(4):460-467
Protease from a strain of Serratia contained one gram atom of zinc ion per mole and the zinc ion was essential for the activity. Also zinc-free apoenzyme was isolated as a crystalline form from the native-enzyme. Several metalloenzymes were prepared by the addition of corresponding metal ions to the apoenzyme. Studies on activities toward the hydrolysis of casein showed that relative activities of native- (zinc), cobalt- and manganese-enzyme were 1.0, 1.2 and 0.8, respectively. Toward the hydrolysis of hippurylleucinamide, however, specific activity of cobalt-enzyme was about 10 times that of the native- (zinc-) enzyme. Spectroscopic studies did not reveal any significant differences in conformations among native-enzyme, apoenzyme and the other metalloenzymes. 相似文献
78.
Yoshihisa Tanaka Masanobu Kirita Yuko Abe Satoshi Miyata Motoyuki Tagashira Tomomasa Kanda 《Bioscience, biotechnology, and biochemistry》2013,77(7):1140-1146
Seven new O-methylated theaflavins (TFs) were synthesized by using O-methyltransferase from an edible mushroom. Using TFs and O-methylated TFs, metabolic stability in pooled human liver S9 fractions and inhibitory effect on H2O2-induced oxidative damage in human HepG2 cells were investigated. In O-methylation of theaflavin 3′-O-gallate (TF3′G), metabolic stability was potentiated by an increase in the number of introduced methyl groups. O-methylation of TF3,3′G did not affect metabolic stability, which was likely because of a remaining 3-O-galloyl group. The inhibitory effect on oxidative damage was assessed by measuring the viability of H2O2-damaged HepG2 cells treated with TFs and O-methylated TFs. TF3,3′G and O-methylated TFs increased cell viabilities significantly compared with DMSO, which was the compound vehicle (p?<?0.05), and improved to approximately 100%. Only TF3′G did not significantly increase cell viability. It was suggested that the inhibitory effect on H2O2-induced oxidative damage was potentiated by O-methylation or O-galloylation of TFs. 相似文献
79.
Takayoshi Suzuki Yuki Kasuya Yukihiro Itoh Yosuke Ota Peng Zhan Kaori Asamitsu Hidehiko Nakagawa Takashi Okamoto Naoki Miyata 《PloS one》2013,8(7)
To find histone deacetylase 3 (HDAC3)-selective inhibitors, a series of 504 candidates was assembled using “click chemistry”, by reacting nine alkynes bearing a zinc-binding group with 56 azide building blocks in the presence of Cu(I) catalyst. Screening of the 504-member triazole library against HDAC3 and other HDAC isozymes led to the identification of potent and selective HDAC3 inhibitors T247 and T326. These compounds showed potent HDAC3 inhibition with submicromolar IC50s, whereas they did not strongly inhibit other isozymes. Compounds T247 and T326 also induced a dose-dependent selective increase of NF-κB acetylation in human colon cancer HCT116 cells, indicating selective inhibition of HDAC3 in the cells. In addition, these HDAC3-selective inhibitors induced growth inhibition of cancer cells, and activated HIV gene expression in latent HIV-infected cells. These findings indicate that HDAC3-selective inhibitors are promising candidates for anticancer drugs and antiviral agents. This work also suggests the usefulness of the click chemistry approach to find isozyme-selective HDAC inhibitors. 相似文献
80.
Naoko Minatani Mina Waraya Keishi Yamashita Mariko Kikuchi Hideki Ushiku Ken Kojo Akira Ema Hiroshi Nishimiya Yoshimasa Kosaka Hiroshi Katoh Norihiko Sengoku Hirokazu Tanino David Sidransky Masahiko Watanabe 《PloS one》2016,11(1)
Using pharmacological unmasking microarray, we identified promoter DNA methylation of cysteine dioxygenase 1 (CDO1) gene in human cancer. In this study, we assessed the clinicopathological significance of CDO1 methylation in primary breast cancer (BC) with no prior chemotherapy. The CDO1 DNA methylation was quantified by TaqMan methylation specific PCR (Q-MSP) in 7 BC cell lines and 172 primary BC patients with no prior chemotherapy. Promoter DNA of the CDO1 gene was hypermethylated in 6 BC cell lines except SK-BR3, and CDO1 gene expression was all silenced at mRNA level in the 7 BC cell lines. Quantification of CDO1 methylation was developed using Q-MSP, and assessed in primary BC. Among the clinicopathologic factors, CDO1 methylation level was not statistically significantly associated with any prognostic factors. The log-rank plot analysis elucidated that the higher methylation the tumors harbored, the poorer prognosis the patients exhibited. Using the median value of 58.0 as a cut-off one, disease specific survival in BC patients with CDO1 hypermethylation showed significantly poorer prognosis than those with hypomethylation (p = 0.004). Multivariate Cox proportional hazards model identified that CDO1 hypermethylation was prognostic factor as well as Ki-67 and hormone receptor status. The most intriguingly, CDO1 hypermethylation was of robust prognostic relevance in triple negative BC (p = 0.007). Promoter DNA methylation of CDO1 gene was robust prognostic indicator in primary BC patients with no prior chemotherapy. Prognostic relevance of the CDO1 promoter DNA methylation is worthy of being paid attention in triple negative BC cancer. 相似文献