全文获取类型
收费全文 | 445篇 |
免费 | 45篇 |
出版年
2023年 | 2篇 |
2022年 | 3篇 |
2021年 | 15篇 |
2020年 | 9篇 |
2019年 | 7篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 14篇 |
2015年 | 13篇 |
2014年 | 15篇 |
2013年 | 56篇 |
2012年 | 17篇 |
2011年 | 22篇 |
2010年 | 19篇 |
2009年 | 7篇 |
2008年 | 25篇 |
2007年 | 21篇 |
2006年 | 29篇 |
2005年 | 38篇 |
2004年 | 24篇 |
2003年 | 19篇 |
2002年 | 15篇 |
2001年 | 8篇 |
2000年 | 4篇 |
1999年 | 12篇 |
1998年 | 14篇 |
1997年 | 7篇 |
1996年 | 3篇 |
1995年 | 8篇 |
1994年 | 10篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 6篇 |
1989年 | 8篇 |
1988年 | 7篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
排序方式: 共有490条查询结果,搜索用时 62 毫秒
81.
High-resolution molecular and antigen structure of the VP8* core of a sialic acid-independent human rotavirus strain 下载免费PDF全文
Monnier N Higo-Moriguchi K Sun ZY Prasad BV Taniguchi K Dormitzer PR 《Journal of virology》2006,80(3):1513-1523
The most intensively studied rotavirus strains initially attach to cells when the "heads" of their protruding spikes bind cell surface sialic acid. Rotavirus strains that cause disease in humans do not bind this ligand. The structure of the sialic acid binding head (the VP8* core) from the simian rotavirus strain RRV has been reported, and neutralization epitopes have been mapped onto its surface. We report here a 1.6-A resolution crystal structure of the equivalent domain from the sialic acid-independent rotavirus strain DS-1, which causes gastroenteritis in humans. Although the RRV and DS-1 VP8* cores differ functionally, they share the same galectin-like fold. Differences between the RRV and DS-1 VP8* cores in the region that corresponds to the RRV sialic acid binding site make it unlikely that DS-1 VP8* binds an alternative carbohydrate ligand in this location. In the crystals, a surface cleft on each DS-1 VP8* core binds N-terminal residues from a neighboring molecule. This cleft may function as a ligand binding site during rotavirus replication. We also report an escape mutant analysis, which allows the mapping of heterotypic neutralizing epitopes recognized by human monoclonal antibodies onto the surface of the VP8* core. The distribution of escape mutations on the DS-1 VP8* core indicates that neutralizing antibodies that recognize VP8* of human rotavirus strains may bind a conformation of the spike that differs from those observed to date. 相似文献
82.
Yu Hasegawa Kenyu Hayashi Yushin Takemoto Cao Cheng Koki Takane Bowen Lin Yoshihiro Komohara Shokei Kim-Mitsuyama 《Cardiovascular diabetology》2017,16(1):154
Background
The potential of anti-aging effect of DPP-4 inhibitors is unknown. This study was performed to determine whether linagliptin, a DPP-4 inhibitor, could protect against premature aging in klotho?/? mice.Methods
Klotho?/? mice exhibit multiple phenotypes resembling human premature aging, including extremely shortened life span, cognitive impairment, hippocampal neurodegeneration, hair loss, muscle atrophy, hypoglycemia, etc. To investigate the effect of linagliptin on these aging-related phenotypes, male klotho?/? mice were divided into two groups: (1) control group fed the standard diet, and (2) linagliptin group fed the standard diet containing linagliptin. Treatment with linagliptin was performed for 4 weeks. The effect of linagliptin on the above mentioned aging-related phenotypes was examined.Results
Body weight of klotho?/? mice was greater in linagliptin group than in control group (11.1 ± 0.3 vs 9.9 ± 0.3 g; P < 0.01), which was associated with greater gastrocnemius muscle weight (P < 0.01) and greater kidney weight (P < 0.05) in linagliptin group. Thus, linagliptin significantly prevented body weight loss in klotho?/? mice. Survival rate of klotho?/? mice was greater in linagliptin group (93%) compared to control group (67%), although the difference did not reach statistical significance (P = 0.08). None of linagliptin-treated klotho?/? mice had alopecia during the treatment (P < 0.05 vs control klotho?/? mice). Latency of klotho?/? mice in passive avoidance test was larger in linagliptin group than in control group (P < 0.05), indicating the amelioration of cognitive impairment by linagliptin. Cerebral blood flow of klotho?/? mice was larger in linagliptin group than in control group (P < 0.01), being associated with greater cerebral phospho-eNOS levels (P < 0.05) in linagliptin group. Neuronal cell number in hippocampal CA1 region was greater in linagliptin group than in control group (P < 0.05). Linagliptin group had greater cerebral phospho-Akt (P < 0.05) and phospho-CREB (P < 0.05) than control group. Thus, linagliptin ameliorated brain aging in klotho?/? mice. The degree of hypoglycemia in klotho?/? mice was less in linagliptin group than in control group, as estimated by the findings of OGTT.Conclusions
Out work provided the evidence that DPP-4 inhibition with linagliptin slowed the progression of premature aging in klotho?/? mice, and provided a novel insight into the potential role of DPP-4 in the mechanism of premature aging.83.
Teramura N Tanaka K Iijima K Hayashida O Suzuki K Hattori S Irie S 《Journal of bacteriology》2011,193(12):3049-3056
The collagenase gene was cloned from Grimontia (Vibrio) hollisae 1706B, and its complete nucleotide sequence was determined. Nucleotide sequencing showed that the open reading frame was 2,301 bp in length and encoded an 84-kDa protein of 767 amino acid residues. The deduced amino acid sequence contains a putative signal sequence and a zinc metalloprotease consensus sequence, the HEXXH motif. G. hollisae collagenase showed 60 and 59% amino acid sequence identities to Vibrio parahaemolyticus and Vibrio alginolyticus collagenase, respectively. In contrast, this enzyme showed < 20% sequence identity with Clostridium histolyticum collagenase. When the recombinant mature collagenase, which consisted of 680 amino acids with a calculated molecular mass of 74 kDa, was produced by the Brevibacillus expression system, a major gelatinolytic protein band of ~ 60 kDa was determined by zymographic analysis. This result suggested that cloned collagenase might undergo processing after secretion. Moreover, the purified recombinant enzyme was shown to possess a specific activity of 5,314 U/mg, an ~ 4-fold greater activity than that of C. histolyticum collagenase. 相似文献
84.
Klippel B Lochner A Bruce DC Davenport KW Detter C Goodwin LA Han J Han S Land ML Mikhailova N Nolan M Pennacchio L Pitluck S Tapia R Woyke T Wiebusch S Basner A Abe F Horikoshi K Keller M Antranikian G 《Journal of bacteriology》2011,193(17):4547-4548
Glaciecola sp. strain 4H-3-7+YE-5 was isolated from subseafloor sediments at Suruga Bay in Japan and is capable of efficiently hydrolyzing cellulose and xylan. The complete genome sequence of Glaciecola sp. 4H-3-7+YE-5 revealed several genes encoding putatively novel glycoside hydrolases, offering a high potential for plant biomass degradation. 相似文献
85.
Klippel B Lochner A Bruce DC Davenport KW Detter C Goodwin LA Han J Han S Hauser L Land ML Nolan M Ovchinnikova G Pennacchio L Pitluck S Tapia R Woyke T Wiebusch S Basner A Abe F Horikoshi K Keller M Antranikian G 《Journal of bacteriology》2011,193(17):4545-4546
Two members of the family Flavobacteriaceae were isolated from subseafloor sediments using artificial seawater with cellulose, xylan, and chitin as the sole carbon and energy sources. Here, we present the complete genome sequences of Krokinobacter sp. strain 4H-3-7-5 and Lacinutrix sp. strain 5H-3-7-4, which both encode putatively novel enzymes involved in cellulose, hemicellulose, and chitin metabolism. 相似文献
86.
87.
88.
Bacillus No. C–59–2 isolated from soil produced a xylanase in alkaline media. The characteristic point of this bacteria was especially good growth in alkaline media, and no growth was observed in neutral media such as nutrient broth. The xylanase of this bacteria was purified by CM-celluIose, hydroxyl apatite and Sephadex G–75 columns. The enzyme was most active at pH 5.5~9 which was much broader and higher than those of other xylanases. The sedimentation constant was about 3.5 S and isoelectric point was pH 6.3. The enzyme was most stable at pH 7 and calcium ion was effective to stabilize the enzyme. The enzyme activity was inhibited by Hg2+, Ag2+ and Cd2 + Maximum hydrolysis rate of xylan by the enzyme was about 40%. The enzyme split xylan and yielded xylobiose and higher oligosaccharides. Therefore, this enzyme is considered to be a type of endo-xylanase. 相似文献
89.
A cyclodextrin glucanotransferase (CGTase) from Bacillus clarkii 7364 converts starch into gamma-cyclodextrin (gamma-CD) with high specificity. Comparison of the deduced amino acid sequence of this CGTase with those of other typical CGTases revealed that several amino acids are deleted or substituted with others at several subsites. Of these amino acids, Ala223 at subsite +2 and Gly255 at subsite +3 in the acceptor site of the enzyme were replaced by several amino acids through site-directed mutagenesis. The replacement of Ala223 by lysine, arginine and histidine strongly enhanced the gamma-CD-forming activity in the neutral pH range. On the other hand, all mutants obtained on replacing Gly255 with the above amino acids showed significant decreases in the gamma-CD-forming activity. Taking into account both the kinetic parameters and pKa values of the side chains of the three basic amino acids, the protonation state of the amino groups in their side chains at subsite +2 seems to enhance the hydrogen bonding interaction between these basic amino acids and the glucose residues of linear oligosaccharides. The enhancement of the interaction may play an important role by helping the substrate reach subsite +1, hence increasing the gamma-CD-forming activity and kcat value. 相似文献
90.
Microbial Community in Black Rust Exposed to Hot Ridge Flank Crustal Fluids 总被引:1,自引:0,他引:1 下载免费PDF全文
Satoshi Nakagawa Fumio Inagaki Yohey Suzuki Bjrn Olav Steinsbu Mark Alexander Lever Ken Takai Bert Engelen Yoshihiko Sako Charles Geoffrey Wheat Koki Horikoshi Integrated Ocean Drilling Program Expedition Scientists 《Applied microbiology》2006,72(10):6789-6799
During Integrated Ocean Drilling Program Expedition 301, we obtained a sample of black rust from a circulation obviation retrofit kit (CORK) observatory at a borehole on the eastern flank of Juan de Fuca Ridge. Due to overpressure, the CORK had failed to seal the borehole. Hot fluids from oceanic crust had discharged to the overlying bottom seawater and resulted in the formation of black rust analogous to a hydrothermal chimney deposit. Both culture-dependent and culture-independent analyses indicated that the black-rust-associated community differed from communities reported from other microbial habitats, including hydrothermal vents at seafloor spreading centers, while it shared phylotypes with communities previously detected in crustal fluids from the same borehole. The most frequently retrieved sequences of bacterial and archaeal 16S rRNA genes were related to the genera Ammonifex and Methanothermococcus, respectively. Most phylotypes, including phylotypes previously detected in crustal fluids, were isolated in pure culture, and their metabolic traits were determined. Quantification of the dissimilatory sulfite reductase (dsrAB) genes, together with stable sulfur isotopic and electron microscopic analyses, strongly suggested the prevalence of sulfate reduction, potentially by the Ammonifex group of bacteria. Stable carbon isotopic analyses suggested that the bulk of the microbial community was trophically reliant upon photosynthesis-derived organic matter. This report provides important insights into the phylogenetic, physiological, and trophic characteristics of subseafloor microbial ecosystems in warm ridge flank crusts. 相似文献