全文获取类型
收费全文 | 136篇 |
免费 | 8篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 5篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 5篇 |
2013年 | 9篇 |
2012年 | 7篇 |
2011年 | 8篇 |
2010年 | 8篇 |
2009年 | 13篇 |
2008年 | 12篇 |
2007年 | 14篇 |
2006年 | 4篇 |
2005年 | 4篇 |
2004年 | 8篇 |
2003年 | 6篇 |
2002年 | 8篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 6篇 |
1997年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1991年 | 1篇 |
1988年 | 1篇 |
1977年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有144条查询结果,搜索用时 46 毫秒
1.
It was ascertained that thymidine-3H added exogenously is incorporated periodically into the nucleus of the fertilized and the artificially activated eggs of Pseudocentrotus, Temnopleurus and Anthocidaris. Eggs stimulated insufficiently with butyric acid did not show any enhancement of incorporation of thymidine-3H. However, repetition of an insufficient stimulation induced incorporation of thymidine to some degree, although no visible cortical changes occurred. 相似文献
2.
3.
4.
Hori H Nagasawa H Ishibashi M Uto Y Hirata A Saijo K Ohkura K Kirk KL Uehara Y 《Bioorganic & medicinal chemistry》2002,10(10):3257-3265
A series of 2-hydroxyarylidene-4-cyclopentene-1,3-diones were designed, synthesized, and evaluated with respect to protein tyrosine kinase (PTK) inhibition, mitochondrial toxicity, and antitumor activity. Our results show that the cyclopentenedione-derived TX-1123 is a more potent antitumor tyrphostin and also shows lower mitochondrial toxicity than the malononitrile-derived AG17, a potent antitumor tyrphostin. The O-methylation product of TX-1123 (TX-1925) retained its tyrphostin-like properties, including mitochondrial toxicity and antitumor activities. However, the methylation product of AG17 (TX-1927) retained its tyrphostin-like antitumor activities, but lost its mitochondrial toxicity. Our comprehensive evaluation of these agents with respect to protein tyrosine kinase inhibition, mitochondrial inhibition, antitumor activity, and hepatotoxicity demonstrates that PTK inhibitors TX-1123 and TX-1925 are more promising candidates for antitumor agents than tyrphostin AG17. 相似文献
5.
The cooperative binding of monomeric ligands to a long lattice of a linear polymer with complete or partial steric hindrance is treated using a matrix method. Results and typical calculations of the model are represented. Non-saturated cooperative binding as well as two-step (biphasic) binding isotherms can be interpreted by the steric hindrance model. This is applicable to the analysis of the binding of surfactants to polymer. The usefulness and the limitation also are discussed. 相似文献
6.
Sequential aldol condensation catalyzed by hyperthermophilic 2-deoxy-d-ribose-5-phosphate aldolase 总被引:1,自引:0,他引:1
Sakuraba H Yoneda K Yoshihara K Satoh K Kawakami R Uto Y Tsuge H Takahashi K Hori H Ohshima T 《Applied and environmental microbiology》2007,73(22):7427-7434
Genes encoding 2-deoxy-d-ribose-5-phosphate aldolase (DERA) homologues from two hyperthermophiles, the archaeon Pyrobaculum aerophilum and the bacterium Thermotoga maritima, were expressed individually in Escherichia coli, after which the structures and activities of the enzymes produced were characterized and compared with those of E. coli DERA. To our surprise, the two hyperthermophilic DERAs showed much greater catalysis of sequential aldol condensation using three acetaldehydes as substrates than the E. coli enzyme, even at a low temperature (25 degrees C), although both enzymes showed much less 2-deoxy-d-ribose-5-phosphate synthetic activity. Both the enzymes were highly resistant to high concentrations of acetaldehyde and retained about 50% of their initial activities after a 20-h exposure to 300 mM acetaldehyde at 25 degrees C, whereas the E. coli DERA was almost completely inactivated after a 2-h exposure under the same conditions. The structure of the P. aerophilum DERA was determined by X-ray crystallography to a resolution of 2.0 A. The main chain coordinate of the P. aerophilum enzyme monomer was quite similar to those of the T. maritima and E. coli enzymes, whose crystal structures have already been solved. However, the quaternary structure of the hyperthermophilic enzymes was totally different from that of the E. coli DERA. The areas of the subunit-subunit interface in the dimer of the hyperthermophilic enzymes are much larger than that of the E. coli enzyme. This promotes the formation of the unique dimeric structure and strengthens the hydrophobic intersubunit interactions. These structural features are considered responsible for the extremely high stability of the hyperthermophilic DERAs. 相似文献
7.
Induction of potent CD8+ T-cell responses by novel biodegradable nanoparticles carrying human immunodeficiency virus type 1 gp120
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The mainstream of recent anti-AIDS vaccines is a prime/boost approach with multiple doses of the target DNA of human immunodeficiency virus type 1 (HIV-1) and recombinant viral vectors. In this study, we have attempted to construct an efficient protein-based vaccine using biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles (NPs), which are capable of inducing potent cellular immunity. A significant expansion of CD8+ T cells specific to the major histocompatibility complex class I-restricted gp120 epitope was observed in mice intranasally immunized once with gp120-carrying NPs but not with gp120 alone or gp120 together with the B-subunit of cholera toxin. Both the gp120-encapsulating and -immobilizing forms of NPs could induce antigen-specific spleen CD8+ T cells having a functional profile of cytotoxic T lymphocytes. Long-lived memory CD8+ T cells could also be elicited. Although a substantial decay in the effector memory T cells was observed over time in the immunized mice, the central memory T cells remained relatively constant from day 30 to day 238 after immunization. Furthermore, the memory CD8+ T cells rapidly expanded with boosting with the same immunogen. In addition, gamma-PGA NPs were found to be a much stronger inducer of antigen-specific CD8+ T-cell responses than nonbiodegradable polystyrene NPs. Thus, gamma-PGA NPs carrying various HIV-1 antigens may have great potential as a novel priming and/or boosting tool in current vaccination regimens for the induction of cellular immune responses. 相似文献
8.
The origin of multi-exponential fluorescence decay property of tryptophan (Trp) in protein has been in controversy, and dielectric relaxation is thought to be one of the most plausible candidates of that origin. In this study, we studied melittin-calmodulin interaction on the concept of dielectric relaxation by spectrally and time-resolved fluorescence spectroscopy. Trp residue in melittin demonstrated drastic change in its dielectric relaxation rate and scale by binding with calmodulin. Expected change of relaxation rate suggested that dielectric relaxation accounts for multi-exponential property of fluorescence decay. We also examined the time variation of radiative and non-radiative decay rates. That result demonstrated the distinct difference profiles of non-radiative decay rate of Trp in melittin and the complex. 相似文献
9.
10.
Uto T Tsujimura K Uchijima M Seto S Nagata T Suda T Chida K Nakamura H Koide Y 《FEMS immunology and medical microbiology》2011,61(2):189-196
Heat shock protein 70 (HSP70) is a member of a highly conserved superfamily of intracellular chaperones called stress proteins that can activate innate and adaptive immune responses. We evaluated the effect of a fusion DNA vaccine that encoded mycobacterial HSP70 and MPT51, a major secreted protein of Mycobacterium tuberculosis. Spleen cells from mice immunized with fusion DNA of full-length HSP70 and MPT51 produced a higher amount of interferon-γ (IFN-γ) in response to the CD4+, but not the CD8+ T-cell epitope peptide on MPT51 than those from mice immunized with MPT51 DNA. Furthermore, because HSP70 comprises the N-terminal ATPase domain and the C-terminal peptide-binding domain, we attempted to identify the domain responsible for its enhancing effect. The fusion DNA vaccine that encoded the C-terminal domain of HSP70 and MPT51 induced a higher MPT51-specific IFN-γ production by CD4+ T cells than the vaccine that encoded MPT51 alone, whereas that with the N-terminal domain did not. Similar results were obtained by immunization with the fusion proteins. These results suggest that the DNA vaccine that encodes a chimeric antigen molecule fused with mycobacterial HSP70, especially with its C-terminal domain, can induce a stronger antigen-specific T-helper cell type 1 response than antigen DNA alone. 相似文献