全文获取类型
收费全文 | 1181篇 |
免费 | 58篇 |
出版年
2021年 | 12篇 |
2020年 | 7篇 |
2019年 | 5篇 |
2018年 | 12篇 |
2017年 | 11篇 |
2016年 | 17篇 |
2015年 | 34篇 |
2014年 | 36篇 |
2013年 | 139篇 |
2012年 | 44篇 |
2011年 | 58篇 |
2010年 | 35篇 |
2009年 | 42篇 |
2008年 | 64篇 |
2007年 | 80篇 |
2006年 | 68篇 |
2005年 | 75篇 |
2004年 | 74篇 |
2003年 | 56篇 |
2002年 | 78篇 |
2001年 | 15篇 |
2000年 | 11篇 |
1999年 | 13篇 |
1998年 | 11篇 |
1997年 | 7篇 |
1996年 | 12篇 |
1995年 | 10篇 |
1994年 | 12篇 |
1993年 | 19篇 |
1992年 | 10篇 |
1991年 | 10篇 |
1990年 | 7篇 |
1989年 | 15篇 |
1988年 | 12篇 |
1987年 | 6篇 |
1986年 | 10篇 |
1985年 | 7篇 |
1984年 | 12篇 |
1983年 | 13篇 |
1982年 | 8篇 |
1981年 | 8篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1978年 | 7篇 |
1976年 | 5篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1969年 | 4篇 |
1961年 | 4篇 |
排序方式: 共有1239条查询结果,搜索用时 156 毫秒
101.
Tsukasa Tameyasu Naokata Ishii Noboru Oishi Mitsuyo Shimada Ibuki Shirakawa Tsuyoshi Akimoto Naoto Yamamoto Shoichi Kosuge Haruo Sugi 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》1998,120(4):731-736
To investigate characteristics of ATP-dependent sliding of a non-muscle cell myosin, obtained from a cellular slime mold Dictyostelium discoideum, on actin filament, we prepared hybrid thick filaments, in which Dictyostelium myosin was regularly arranged around paramyosin filaments obtained from a molluscan smooth muscle. A single to a few hybrid filaments were attached to a polystyrene bead (diameter, 4.5 μm; specific gravity, 1.5), and the filaments were made to slide on actin filament arrays (actin cables) in the internodal cell of an alga Chara corallina, mounted on the rotor of a centrifuge microscope. The filament-attached bead was observed to move with a constant velocity under a constant external load for many seconds. The steady-state force–velocity relation of Dictyostelium myosin sliding on actin cables was hyperbolic in shape except for large loads ≤0.7–0.8 P0, being qualitatively similar to that of skeletal muscle fibres, despite a considerable variation in the number of myosin molecules interacting with actin cables. Comparison of the P–V curves between Dictyostelium myosin and muscle myosins sliding on actin cables suggests that the time of attachment to actin in a single attachment–detachment cycle is much longer in Dictyostelium myosin than in muscle myosins. 相似文献
102.
103.
Miho Honma Shinji Kudo Noboru Takada Kazuaki Tanaka Tomisato Miura Masaru Hashimoto 《Bioorganic & medicinal chemistry letters》2010,20(2):709-712
Novel fusapyrone analogs, deoxyneofusapyrone and 7-desmethyldeoxyneofusapyrone were isolated from a pathogenic fungus, Verticillium dahliae, which causes Verticillium wilt disease in Helianthus annuus. Spectral analyses revealed that these are 2-pyrone type analogs of deoxyfusapyrone and its 7-desmethyl derivative, respectively. Biological assay disclosed that 10 μg of deoxyneofusapyrone inhibited the growth of MRSA clinical isolate 87-7927. 相似文献
104.
105.
106.
Sayuki Iijima Kentaro Matsuura Tsunamasa Watanabe Koji Onomoto Takashi Fujita Kyoko Ito Etsuko Iio Tomokatsu Miyaki Kei Fujiwara Noboru Shinkai Atsunori Kusakabe Mio Endo Shunsuke Nojiri Takashi Joh Yasuhito Tanaka 《PloS one》2015,10(2)
The levels of expression of interferon-stimulated genes (ISGs) in liver are associated with response to treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV). However, associations between the responses of ISGs to IFN-based therapy and treatment efficacy or interleukin-28B (IL28B) genotype have not yet been determined. Therefore, we investigated the early responses of ISGs and interferon-lambdas (IFN-λs) in peripheral blood mononuclear cells (PBMCs) during PEG-IFN/RBV plus NS3/4 protease inhibitor (PI) therapy. We prospectively enrolled 50 chronic hepatitis C patients with HCV genotype 1, and collected PBMCs at baseline, 8 and 24 h after the initial administration of PEG-IFN/RBV/PI. Levels of mRNAs for selected ISGs and IFN-λs were evaluated by real-time PCR. All 31 patients with a favorable IL28B genotype and 13 of 19 with an unfavorable genotype achieved sustained virological responses (SVR). Levels of mRNA for A20, SOCS1, and SOCS3, known to suppress antiviral activity by interfering with the IFN signaling pathway, as well as IRF1 were significantly higher at 8 h in patients with an unfavorable IL28B genotype than in those with a favorable one (P = 0.007, 0.026, 0.0004, 0.0006, respectively), especially in the non-SVR group. Particularly, the fold-change of IRF1 at 8 h relative to baseline was significantly higher in non-SVR than in SVR cases with an unfavorable IL28B genotype (P = 0.035). In conclusion, levels of several mRNAs of genes suppressing antiviral activity in PBMCs during PEG-IFN/RBV/PI differed according to IL28B genotypes, paralleling treatment efficacy. 相似文献
107.
Hiroko Yamada Kazuaki Takahashi Olline Lim Somana Svay Channarena Chuon Sirany Hok Son Huy Do Mayumi Fujimoto Tomoyuki Akita Noboru Goto Keiko Katayama Masahiro Arai Junko Tanaka 《PloS one》2015,10(8)
Hepatitis E virus (HEV) is a growing public health problem in many countries. In this study, we investigated HEV seroprevalence among the general population in the Siem Reap province, Cambodia, and performed HEV genetic analysis with the aim to develop an HEV prevention strategy. This seroepidemiological cross-sectional study conducted from 2010 to 2014 included 868 participants from four different locations in Siem Reap province, Cambodia. They answered questionnaires and provided blood samples for the analysis of hepatitis virus infections. Among the participants (360 men and 508 women; age range, 7–90 years), the prevalence of anti-HEV IgG was 18.4% (95% confidence interval: 15.9–21.0); HEV RNA was detected in two participants (0.23%) and was classified as genotype 3 and 4. Full-length genome of the genotype 4 isolate, CVS-Sie10, was sequenced; it contained 7,222 nucleotides and three ORFs and demonstrated high sequence identity with the swine China isolates swGX40 (95.57%), SS19 (94.37%), and swDQ (91.94%). Multivariate logistic regression analysis revealed that men, elderly people, and house workers were risk groups significantly associated with the positivity for anti-HEV IgG. This is the first report on the detection of HEV genotype 4 in humans in Cambodia and on the complete genome sequence of HEV genotype 4 from this country. Our study demonstrates that new HEV infection cases occur frequently among the general population in Cambodia, and effective preventive measures are required. 相似文献
108.
A high incidence of oncogenic K-ras mutations is observed in lung adenocarcinoma of human cases and carcinogen-induced animal models. The process of oncogenic K-ras-mediated lung adenocarcinogenesis can be dissected into two parts: pre- and post-K-ras mutation. Adoption of transgenic lines containing a flox-K-rasG12V transgene eliminates the use of chemical carcinogens and enables us to study directly crucial events post-K-ras mutation without considering the cellular events involved with oncogenic K-ras mutation, e.g., distribution and metabolism of chemical carcinogens, DNA repair, and somatic recombination by host factors. We generated two mouse strains C57BL/6J-Ryr2tm1Nobs and A/J-Ryr2tm1Nobs in which K-rasG12V can be transcribed from the cytomegalovirus early enhancer/chicken beta actin promoter in virtually any tissue. Upon K-rasG12V induction in lung epithelial cells by an adenovirus expressing the Cre recombinase, the number of tumors in the C57BL/6J-Ryr2tm1Nobs/+ mouse line was 12.5 times that in the A/J-Ryr2tm1Nobs/+ mouse line. Quantitative trait locus (QTL) analysis revealed that new three modifier loci, D3Mit19, D3Mit45 and D11Mit20, were involved in the differential susceptibility between the two lines. In addition, we found that differential expression of the wild-type K-ras gene, which was genetically turn out to be anti-oncogenic activity on K-rasG12V, could not account for the different susceptibility in our two K-rasG12V-mediated lung tumor models. Thus, we provide a genetic system that enables us to explore new downstream modifiers post-K-ras mutation. 相似文献
109.
Takako Watanabe-Asano Akiko Kuma Noboru Mizushima 《Biochemical and biophysical research communications》2014
Protein synthesis inhibitors such as cycloheximide (CHX) are known to suppress protein degradation including autophagy. The fact that CHX inhibits autophagy has been generally interpreted to indicate that newly synthesized protein is indispensable for autophagy. However, CHX is also known to increase the intracellular level of amino acids and activate mTORC1 activity, a master negative regulator of autophagy. Accordingly, CHX can affect autophagic activity through inhibition of de novo protein synthesis and/or modulation of mTORC1 signaling. In this study, we investigated the effects of CHX on autophagy using specific autophagy markers. We found that CHX inhibited starvation-induced autophagy but not Torin1-induced autophagy. CHX also suppressed starvation-induced puncta formation of GFP-ULK1, an early-step marker of the autophagic process which is regulated by mTORC1. CHX activated mTORC1 even under autophagy-inducible starvation conditions. Finally, the inhibitory effect of CHX on starvation-induced autophagy was cancelled by the mTOR inhibitor Torin1. These results suggest that CHX inhibits starvation-induced autophagy through mTORC1 activation and also that autophagy does not require new protein synthesis at least in the acute phase of starvation. 相似文献
110.