全文获取类型
收费全文 | 2906篇 |
免费 | 153篇 |
出版年
2023年 | 5篇 |
2022年 | 7篇 |
2021年 | 46篇 |
2020年 | 18篇 |
2019年 | 37篇 |
2018年 | 49篇 |
2017年 | 41篇 |
2016年 | 72篇 |
2015年 | 89篇 |
2014年 | 141篇 |
2013年 | 174篇 |
2012年 | 205篇 |
2011年 | 215篇 |
2010年 | 125篇 |
2009年 | 116篇 |
2008年 | 192篇 |
2007年 | 171篇 |
2006年 | 167篇 |
2005年 | 171篇 |
2004年 | 192篇 |
2003年 | 190篇 |
2002年 | 175篇 |
2001年 | 23篇 |
2000年 | 25篇 |
1999年 | 28篇 |
1998年 | 45篇 |
1997年 | 35篇 |
1996年 | 28篇 |
1995年 | 43篇 |
1994年 | 17篇 |
1993年 | 22篇 |
1992年 | 17篇 |
1991年 | 21篇 |
1990年 | 17篇 |
1989年 | 9篇 |
1988年 | 11篇 |
1987年 | 15篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 14篇 |
1983年 | 12篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 8篇 |
1977年 | 3篇 |
1974年 | 5篇 |
1973年 | 3篇 |
1972年 | 4篇 |
排序方式: 共有3059条查询结果,搜索用时 15 毫秒
91.
Yasuhiro Ishii Kaori Shintani-IshidaKen-ichi Yoshida 《Biochemical and biophysical research communications》2013
We investigated the role of the astrocytic and neuronal hemichannels (HCs) in the spread of cortical neuronal death in a rat cortical injury model. Over time (by 6 h), propidium iodide (PI)-positive cells with labeling either with anti-neuron specific enolase or anti-parvalbumin (indicating GABAnergic interneurons) antibody spread in the deep cortical layers adjacent to the injury and co-localized with activated μ-calpain. Connexin (Cx)-43, glial fibrillary acidic protein (GFAP), activated μ-calpain and α-fodrin breakdown product (FBP) increased post-injury, peaking at 1 h, in the injury and adjacent areas. GFAP-Cx43-positive reactivated astrocytes exhibited similar distribution to the dead neurons. Cx43 and Cx36 primarily comprise HCs in the astrocyte and neuron, respectively. Ethidium bromide (EtBr) uptake was enhanced post-injury, and confirmed in the Cx43- and Cx36-positive cells. A Cx43-HC inhibitor Gap26 prevented the opening of the Cx43-HC and Cx36-HC, μ-calpain activation, α-fodrin proteolysis and death in the deep cortical neurons. Collectively, opening of the astrocytic Cx43-HC and neuronal Cx36-HC would induce the regional spread of cortical neuronal death through μ-calpain activation in the rat brain injury model. 相似文献
92.
Yoshihiro Kato Motoji Kawasaki Tomohiro Nigo Shunya Nakamura Akira Fusano Yasuhiro Teranishi Mari N. Ito Takaaki Sumiyoshi 《Bioorganic & medicinal chemistry》2013,21(18):5851-5854
A series of 2,3-disubstituted pyridines were synthesized and evaluated for their PDE4 inhibitory activity. We successfully modified undesirable cyano group of initial lead compound 2 to 4-pyridyl group with improvement of in vitro efficacy and optimized the position of nitrogen atoms in pyridine moiety and alkylene linker. The most potent compound showed significant efficacy in animal models of asthma and inflammation. 相似文献
93.
Bryan D. Yestrepsky Yuanxi Xu Meghan E. Breen Xiaoqin Li Walajapet G. Rajeswaran Jenny G. Ryu Roderick J. Sorenson Yasuhiro Tsume Michael W. Wilson Wenpeng Zhang Duxin Sun Hongmin Sun Scott D. Larsen 《Bioorganic & medicinal chemistry》2013,21(7):1880-1897
Resistance to antibiotics is an increasingly dire threat to human health that warrants the development of new modes of treating infection. We recently identified 1 (CCG-2979) as an inhibitor of the expression of streptokinase, a critical virulence factor in Group A Streptococcus that endows blood-borne bacteria with fibrinolytic capabilities. In this report, we describe the synthesis and biological evaluation of a series of novel 5,6-dihydrobenzo[h]quinazolin-4(3H)-one analogs of 1 undertaken with the goal of improving the modest potency of the lead. In addition to achieving an over 35-fold increase in potency, we identified structural modifications that improve the solubility and metabolic stability of the scaffold. The efficacy of two new compounds 12c (CCG-203592) and 12k (CCG-205363) against biofilm formation in Staphylococcus aureus represents a promising additional mode of action for this novel class of compounds. 相似文献
94.
Sawao Murao Yasuhiro Shimizu Masaru Kameda Toyokazu Nishino 《Bioscience, biotechnology, and biochemistry》2013,77(12):3075-3077
Several analogs modifying the 6-methoxy-2-methoxymethyl-3-(3,4-methyienedioxyphenyl)-1,4-benzodioxan-7-yl group of haedoxans were synthesized and their insecticidal activity was examined. 2-(2,6-Dimethoxyphenoxy)-1-hydroxy-6-(2-methoxy-5-methoxyethoxyphenyl)-3,7-dioxabicyclo-[3.3.0]octane, which lacked the 3-(3,4-methylenedioxybenzyloxy) moiety of the benzodioxanyl group, was not insecticidal, but caused prolonged paralysis of the housefly. A compound replacing the 6-(2-methoxy-5-methoxyethoxyphenyl) by 6-(5-butoxy-2-methoxyphenyl) exhibited insecticidal activity comparable to one thirty-thousandth of that of haedosan A. It became evident that the 1,4-benzodioxane framework charging the 3-(3,4-methylenedioxy)phenyl group is important for the insecticidal activity of haedoxans. 相似文献
95.
96.
The 2,3-Dihydro-lH-pyrrolo[l,2-a]indole ring system was synthesised by the condensation reaction of toluquinone and 2-cyanomethylenepyrrolidine. 相似文献
97.
Yasuhiro Arii Kohei Butsusihta Shin-Ichi Fukuoka 《Bioscience, biotechnology, and biochemistry》2013,77(6):978-985
Annexin A4 (Anx4) is a cytosolic calcium-binding protein with four repeat domains, each containing one calcium-binding site (CBS). The protein interacts with the phospholipid membrane through the CBS-coordinated calcium ion, although the role of each CBS in the calcium-dependent association is unclear. To determine the role of each CBS, 15 CBS-abolished variants were produced in various combinations by substitution of a calcium-liganding residue on each CBS by Ala. Various mutant combinations produced different influences on calcium-dependent membrane-binding behavior and on the sodium-dependent dissociation of membrane-bound Anx4. Our data suggest the interaction of Anx4 with the lipid membrane consists of strong and weak interactions. CBSs I and IV mediate formation of strong interactions, while CBSs II and III are important for weak interactions. We also suggest Anx4 binds the lipid membrane through CBSs I and IV in the cytoplasmic fluids. 相似文献
98.
Yasuhiro Yamada Hiroshi Noda Hirosuke Okada 《Bioscience, biotechnology, and biochemistry》2013,77(9):2201-2203
Excellent l-proline producers were screened for among sulfaguanidine resistant mutants derived from three typical l-glutamic acid-producing bacteria: Brevibacterium flavum, B. lactofermentum, and C. glutamicum.The best strain, No. 199, is a sulfaguanidine resistant mutant derived from an isoleucine auxotroph of B. flavum 2247 by nitrosoguanidine. Strain No. 199 produced 35 mg/ml of l-proline after 72 hr of cultivation with 10% glucose as a carbon source. The strain also accumulated purine bases such as adenine, guanine, and hypoxanthine, i.e., degradation products of purine nucleotides. In the mutant, 1.6 ~ 2.0 fold more intracellular ATP was found than that in the parent strain; it is a substrate of glutamate kinase relating to l-proline biosynthesis.On the contrary, the levels of intracellular glutamic acid, a substrate of glutamate kinase, were similar among these strains.It was confirmed that the increment of internal ATP, which was important in the l-proline production mechanism, was very effective in the improvement of l-proline producers. 相似文献
99.
Hirofumi Sakoguchi Tomoya Shintani Hironobu Ishiyama Ryo C. Yanagita Yasuhiro Kawanami 《Bioscience, biotechnology, and biochemistry》2013,77(12):2194-2197
ABSTRACTThe nematocidal activities of the fatty acid esters of d-allose were examined using the larvae of C. elegans. Among the fatty acid esters, 6-O-octanoyl-d-allose (3) showed significant activity. 6-O-octanoyl-d-glucose (5) showed no activity, indicating that the D-allose moiety is essential for the nematocidal activity of 3. A nonhydrolyzable alkoxy analog 6-O-octyl-d-allose (6) also showed activity equivalent to that of 3. 相似文献
100.
Tatsuma Matsutani Takashi Nagai Kazutoshi Kinjyo Yasuhiro Nakanishi 《Wetlands Ecology and Management》2013,21(2):107-115
To reveal the role of tannins in mangroves, tannins in mangrove leaves and the Fe eluted from mangrove soil by adding tannin solutions of different salinity levels was investigated. Leaves of six mangrove and 16 non-mangrove species, and samples of a mangrove floor, Andosol and dark red soil were collected. Results were: (1) Increasing tannic acid concentration to ~50 mM, increased the Fe eluted from mangrove soil to ~20 μgg?1. (2) When a 100 mM tannic acid solution was added, the Fe eluted from mangrove soil was 5.5 times higher than dark red soil. (3) Although elution of Fe from mangrove soil was higher than in Andosol one day after submersion in a 10 mM tannic acid solution, the difference was stable after 2 days. (4) The elution of Fe from all soils significantly decreased with increasing salinity of a 10 mM tannic acid solution. However, the amount from mangrove soil was 6.1 times higher than dark red soil even with 35 ‰ salinity. (5) The tannin content in the mangrove leaves was 99 ± 16 mgg?1 and non-mangrove leaves was 76 ± 19 mgg?1. (6) The Fe eluted from mangrove soil had a positive correlation with the tannin concentrations in the added leaf solution. Tannins in mangrove species promote the elution of Fe from mangrove floor soil even in saline water. Fe complexes were formed when mangrove soil was mixed with leaf tannins suggesting that Fe produced by tannins in mangrove leaves growing in land/sea interfaces likely plays a direct role in marine ecosystems. 相似文献