全文获取类型
收费全文 | 632篇 |
免费 | 91篇 |
国内免费 | 2篇 |
出版年
2022年 | 8篇 |
2021年 | 11篇 |
2019年 | 4篇 |
2018年 | 8篇 |
2017年 | 8篇 |
2016年 | 13篇 |
2015年 | 19篇 |
2014年 | 16篇 |
2013年 | 60篇 |
2012年 | 25篇 |
2011年 | 36篇 |
2010年 | 20篇 |
2009年 | 17篇 |
2008年 | 30篇 |
2007年 | 23篇 |
2006年 | 24篇 |
2005年 | 25篇 |
2004年 | 19篇 |
2003年 | 28篇 |
2002年 | 17篇 |
2001年 | 29篇 |
2000年 | 26篇 |
1999年 | 28篇 |
1998年 | 13篇 |
1997年 | 5篇 |
1996年 | 6篇 |
1995年 | 11篇 |
1994年 | 4篇 |
1993年 | 6篇 |
1992年 | 14篇 |
1991年 | 19篇 |
1990年 | 12篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 8篇 |
1985年 | 11篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1980年 | 4篇 |
1978年 | 7篇 |
1977年 | 4篇 |
1976年 | 5篇 |
1975年 | 13篇 |
1974年 | 6篇 |
1973年 | 8篇 |
1972年 | 6篇 |
1971年 | 5篇 |
1970年 | 8篇 |
1969年 | 8篇 |
排序方式: 共有725条查询结果,搜索用时 62 毫秒
61.
62.
H.S. Gupta J. Seto S. Krauss P. Boesecke H.R.C. Screen 《Journal of structural biology》2010,169(2):183-191
Tendon is a hydrated multi-level fibre composite, in which time-dependent behaviour is well established. Studies indicate significant stress relaxation, considered important for optimising tissue stiffness. However, whilst this behaviour is well documented, the mechanisms associated with the response are largely unknown. This study investigates the sub-structural mechanisms occurring during stress relaxation at both the macro (fibre) and nano (fibril) levels of the tendon hierarchy. Stress relaxation followed a two-stage exponential behaviour, during which structural changes were visible at the fibre and fibril levels. Fibril relaxation and fibre sliding showed a double exponential response, while fibre sliding was clearly the largest contributor to relaxation. The amount of stress relaxation and sub-structural reorganisation increased with increasing load increments, but fibre sliding was consistently the largest contributor to stress relaxation. A simple model of tendon viscoelasticity at the fibril and fibre levels has been developed, capturing this behaviour by serially coupling a Voigt element (collagen fibril), with two Maxwell elements (non-collagenous matrix between fibrils and fibres). This multi-level analysis provides a first step towards understanding how sub-structural interactions contribute to viscoelastic behaviour. It indicates that nano- and micro-scale shearing are significant dissipative mechanisms, and the kinetics of relaxation follows a two-stage exponential decay, well fitted by serially coupled viscoelastic elements. 相似文献
63.
Jian-Hong Wu Qing Li Min-Yi Wu De-Jian Guo Huan-Le Chen Shi-Lin Chen Sai-Wang Seto Alice L.S. Au Christina C.W. Poon George P.H. Leung Simon M.Y. Lee Yiu-Wa Kwan Shun-Wan Chan 《The Journal of nutritional biochemistry》2010,21(7):613-620
We evaluated the vasorelaxation effects of formononetin, an isoflavone/phytoestrogen found abundantly in Astragalus mongholicus Bunge, on rat isolated aorta and the underlying mechanisms involved. Cumulative administration of formononetin, genistein, daidzein and biochanin A relaxed phenylephrine-preconstricted aorta. Formononetin and biochanin A caused a similar magnitude of relaxation whereas daidzein was least potent. Mechanical removal of endothelium, L-NAME (100 μM) and methylene blue (10 μM) suppressed formononetin-induced relaxation. Formononetin increased endothelial nitric oxide (NO) synthase (eNOS), but not inducible NO synthase, activity with an up-regulation of eNOS mRNA and p-eNOSSer1177 protein expression. In endothelium-denuded preparations, formononetin-induced vasorelaxation was significantly reduced by glibenclamide (3 μM) and iberiotoxin (100 nM), and a combination of glibenclamide (3 μM) plus iberiotoxin (100 nM) abolished the relaxation. In contrast, formononetin-elicited endothelium-independent relaxation was not altered by ICI 182,780 (10 μM, an estrogen receptor (ERα/ERβ) antagonist) or mifepristone (10 μM, a progesterone receptor antagonist). In single aortic smooth muscle cells, formononetin caused opening of iberiotoxin-sensitive Ca2+-activated K+ (BKCa) channels and glibenclamide-sensitive adenosine triphosphate (ATP)-dependent K+ (KATP) channels. Thus, our results suggest that formononetin caused vascular relaxation via endothelium/NO-dependent mechanism and endothelium-independent mechanism which involves the activation of BKCa and KATP channels. 相似文献
64.
Philip G Wong Michele A Glozak Thinh V Cao Cyrus Vaziri Edward Seto Mark G Alexandrow 《Cell cycle (Georgetown, Tex.)》2010,9(21):4351-4363
The efficiency of metazoan origins of DNA replication is known to be enhanced by histone acetylation near origins. Although this correlates with increased MCM recruitment, the mechanism by which such acetylation regulates MCM loading is unknown. We show here that Cdt1 induces large-scale chromatin decondensation that is required for MCM recruitment. This process occurs in G1, is suppressed by Geminin and requires HBO1 HAT activity and histone H4 modifications. HDAC11, which binds Cdt1 and replication origins during S phase, potently inhibits Cdt1-induced chromatin unfolding and re-replication, suppresses MCM loading and binds Cdt1 more efficiently in the presence of Geminin. We also demonstrate that chromatin at endogenous origins is more accessible in G1 relative to S phase. These results provide evidence that histone acetylation promotes MCM loading via enhanced chromatin accessibility. This process is regulated positively by Cdt1 and HBO1 in G1 and repressed by Geminin-HDAC11 association with Cdt1 in S phase and represents a novel form of replication licensing control.Key words: Cdt1, HBO1, HDAC11, chromatin, DNA replication 相似文献
65.
Nicoll-Griffith DA Seto C Aubin Y Lévesque JF Chauret N Day S Silva JM Trimble LA Truchon JF Berthelette C Lachance N Wang Z Sturino C Braun M Zamboni R Young RN 《Bioorganic & medicinal chemistry letters》2007,17(2):301-304
Metabolites of the potent DP antagonist, MK-0524, were generated using in vitro systems including hepatic microsomes and hepatocytes. Four metabolites (two hydroxylated diastereomers, a ketone and an acyl glucuronide) were characterized by LC-MS/MS and 1H NMR. Larger quantities of these metabolites were prepared by either organic synthesis or biosynthetically to be used as standards in other studies. The propensity for covalent binding was assessed and was found to be acceptable (<50 pmol-equiv/mg protein). 相似文献
66.
Daud NH Kariwa H Tanikawa Y Nakamura I Seto T Miyashita D Yoshii K Nakauchi M Yoshimatsu K Arikawa J Takashima I 《Microbiology and immunology》2007,51(11):1081-1090
Hokkaido virus (HOKV) is a member of the genus Hantavirus, in the family Bunyaviridae. To investigate HOKV infection in the host Myodes rufocanus, the grey red-backed vole, 199 animals were captured at Tobetsu (October 2004 and July 2005) and Nakagawa (October 2004) in Hokkaido, Japan, for detection of antibody, antigen, and viral RNA. In the surveys in Tobetsu (2004) and Nakagawa (2004), seropositive animals were detected at a frequency of 6.0% (5/84) and 10.4% (5/48), respectively. No seropositive animals were detected in Tobetsu in 2005. Seroprevalence in males in Tobetsu and Nakagawa in 2004 was 25% (1/4) and 45.5% (5/11), respectively, which was higher than in females, at 5.0% (4/80) and 0% (0/37), respectively (P<0.01). These results suggest that male animals play an important role in the maintenance of HOKV in M. rufocanus. Two females were seronegative but viral RNA-positive, indicating that these animals had acute infections before antibody was produced. Another five infected animals in Nakagawa were all male and had high levels of antibodies and viral RNA, suggesting that they had persistent infections. Viral RNA copies in organs of infected animals in Nakagawa were quantified by real-time polymerase chain reaction. Two acutely infected animals had > or = 10 times the number of RNA copies in their lungs compared to those of persistently infected animals. In most cases, lungs or spleen had the highest RNA copy number, regardless of infection status. 相似文献
67.
68.
Mouse Models for Assessing the Protective Efficacy of Lactobacillus gasseri SBT2055 against Helicobacter suis Infection Associated with the Development of Gastric Mucosa‐Associated Lymphoid Tissue Lymphoma
下载免费PDF全文
![点击此处可从《Helicobacter》网站下载免费的PDF全文](/ch/ext_images/free.gif)
69.
Rab GTPases regulating phagosome maturation are differentially recruited to mycobacterial phagosomes
Mycobacterium tuberculosis (M. tb) is an intracellular pathogen that can replicate within infected macrophages. The ability of M. tb to arrest phagosome maturation is believed to facilitate its intracellular multiplication. Rab GTPases regulate membrane trafficking, but details of how Rab GTPases regulate phagosome maturation and how M. tb modulates their localization during inhibiting phagolysosome biogenesis remain elusive. We compared the localization of 42 distinct Rab GTPases to phagosomes containing either Staphylococcus aureus or M. tb. The phagosomes containing S. aureus were associated with 22 Rab GTPases, but only 5 of these showed similar localization kinetics as the phagosomes containing M. tb. The Rab GTPases responsible for phagosome maturation, phagosomal acidification and recruitment of cathepsin D were examined in macrophages expressing the dominant-negative form of each Rab GTPase. LysoTracker staining and immunofluorescence microscopy revealed that Rab7, Rab20 and Rab39 regulated phagosomal acidification and Rab7, Rab20, Rab22b, Rab32, Rab34, Rab38 and Rab43 controlled the recruitment of cathepsin D to the phagosome. These results suggest that phagosome maturation is achieved by a series of interactions between Rab GTPases and phagosomes and that differential recruitment of these Rab GTPases, except for Rab22b and Rab43, to M. tb-containing phagosomes is involved in arresting phagosome maturation and inhibiting phagolysosome biogenesis. 相似文献
70.
Most Escherichia coli O157-serogroup strains are classified as enterohemorrhagic E. coli (EHEC), which is known as an important food-borne pathogen for humans. They usually produce Shiga toxin (Stx) 1 and/or Stx2, and express H7-flagella antigen (or nonmotile). However, O157 strains that do not produce Stxs and express H antigens different from H7 are sometimes isolated from clinical and other sources. Multilocus sequence analysis revealed that these 21 O157:non-H7 strains tested in this study belong to multiple evolutionary lineages different from that of EHEC O157:H7 strains, suggesting a wide distribution of the gene set encoding the O157-antigen biosynthesis in multiple lineages. To gain insight into the gene organization and the sequence similarity of the O157-antigen biosynthesis gene clusters, we conducted genomic comparisons of the chromosomal regions (about 59 kb in each strain) covering the O-antigen gene cluster and its flanking regions between six O157:H7/non-H7 strains. Gene organization of the O157-antigen gene cluster was identical among O157:H7/non-H7 strains, but was divided into two distinct types at the nucleotide sequence level. Interestingly, distribution of the two types did not clearly follow the evolutionary lineages of the strains, suggesting that horizontal gene transfer of both types of O157-antigen gene clusters has occurred independently among E. coli strains. Additionally, detailed sequence comparison revealed that some positions of the repetitive extragenic palindromic (REP) sequences in the regions flanking the O-antigen gene clusters were coincident with possible recombination points. From these results, we conclude that the horizontal transfer of the O157-antigen gene clusters induced the emergence of multiple O157 lineages within E. coli and speculate that REP sequences may involve one of the driving forces for exchange and evolution of O-antigen loci. 相似文献