全文获取类型
收费全文 | 1273篇 |
免费 | 92篇 |
出版年
2023年 | 5篇 |
2022年 | 20篇 |
2021年 | 28篇 |
2020年 | 18篇 |
2019年 | 25篇 |
2018年 | 32篇 |
2017年 | 19篇 |
2016年 | 29篇 |
2015年 | 54篇 |
2014年 | 57篇 |
2013年 | 67篇 |
2012年 | 97篇 |
2011年 | 103篇 |
2010年 | 48篇 |
2009年 | 54篇 |
2008年 | 83篇 |
2007年 | 96篇 |
2006年 | 62篇 |
2005年 | 54篇 |
2004年 | 64篇 |
2003年 | 54篇 |
2002年 | 46篇 |
2001年 | 23篇 |
2000年 | 19篇 |
1999年 | 17篇 |
1998年 | 12篇 |
1997年 | 13篇 |
1996年 | 6篇 |
1995年 | 11篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 14篇 |
1991年 | 18篇 |
1990年 | 10篇 |
1989年 | 7篇 |
1988年 | 5篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1977年 | 3篇 |
1976年 | 8篇 |
1975年 | 5篇 |
1974年 | 3篇 |
1973年 | 5篇 |
1971年 | 8篇 |
1969年 | 3篇 |
1967年 | 3篇 |
1966年 | 5篇 |
排序方式: 共有1365条查询结果,搜索用时 187 毫秒
91.
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
92.
Shinji Kawasaki Masahiro Nagasaku Tsuyoshi Mimura Hitomi Katashima Susumu Ijyuin Takumi Satoh Youichi Niimura 《Applied microbiology》2007,73(23):7796-7798
This report investigates the requirement for CO2 for colony formation by Bifidobacterium species in both anoxic and oxic environments. All tested Bifidobacterium species exhibited difficulty in developing colonies in an atmosphere of 100% N2 but developed well when 1% CO2 was present. In the presence of CO2, the oxygen tolerance of the tested species was not improved. In the absence of CO2, only B. boum, a microaerophilic species, could develop colonies under an N2-based 5% O2 atmosphere, indicating that while CO2 is not an essential factor for colony development, both CO2 and O2 have stimulatory effects on B. boum colony development. 相似文献
93.
Yoshiharu Inoue Wataru Nomura Yoko Takeuchi Takumi Ohdate Shogo Tamasu Atsushi Kitaoka Yoshifumi Kiyokawa Hiroshi Masutani Kazuo Murata Yoshinori Wakai Shingo Izawa Junji Yodoi 《Applied microbiology》2007,73(5):1672-1675
Thioredoxin, an antioxidant protein, is a promising molecule for development of functional foods because it protects the gastric mucosa and reduces the allergenicity of allergens. To establish a method for obtaining an ample amount of yeast thioredoxin, we found here that thioredoxin is released from Saccharomyces cerevisiae by treatment with 20% ethanol. We also found that Japanese sake contains a considerable amount of thioredoxin. 相似文献
94.
Izawa S Ikeda K Ohdate T Inoue Y 《Biochemical and biophysical research communications》2007,353(3):750-755
Recent data suggest that the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subtype plays a pivotal role in the pathogenesis of effective disorders and in the action of antidepressant drugs. After chronic treatment with the antidepressants desipramine or paroxetine, we measured by immunoprecipitation and Western blotting, the changes in the interaction of AMPA receptor subunits with proteins involved in trafficking and/or stabilization of the subunits into synaptic membranes of the hippocampus. Both antidepressants increased the interaction of GluR1 subunit with stargazin and of GluR2/3 with NSF. Paroxetine increased the interaction of GluR1 with Rab4A, and desipramine markedly increased the interaction of GluR1 with SAP97. Paroxetine, but not desipramine, also increased membrane levels of CaMKII, autophosphorylated CaMKII and GluR1 phosphorylated at the CaMKII site. Interactions of GluR1 and GluR2/3 with proteins implicated in AMPA receptor trafficking and with scaffolding proteins appear to account for the enhanced membrane expression of AMPA receptors in the hippocampus after antidepressant treatment. 相似文献
95.
96.
Saito Y Shinkai T Yoshimura Y Takahata H 《Bioorganic & medicinal chemistry letters》2007,17(21):5894-5896
A straightforward synthesis of meso-2,6-diaminopimelic acid (DAP) meso-1 was developed from 1,4-diacetoxycyclohept-2-ene (2) via an oxidative ring cleavage. Subsequently, an enantio-divergent synthesis of (S,S)- and (R,R)-1 was performed using a homochiral monoacetate 7 available from 2 by enzymatic desymmetrization. 相似文献
97.
Genetic and epigenetic alteration among three homoeologous genes of a class E MADS box gene in hexaploid wheat 总被引:4,自引:0,他引:4
下载免费PDF全文
![点击此处可从《The Plant cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Shitsukawa N Tahira C Kassai K Hirabayashi C Shimizu T Takumi S Mochida K Kawaura K Ogihara Y Murai K 《The Plant cell》2007,19(6):1723-1737
Bread wheat (Triticum aestivum) is a hexaploid species with A, B, and D ancestral genomes. Most bread wheat genes are present in the genome as triplicated homoeologous genes (homoeologs) derived from the ancestral species. Here, we report that both genetic and epigenetic alterations have occurred in the homoeologs of a wheat class E MADS box gene. Two class E genes are identified in wheat, wheat SEPALLATA (WSEP) and wheat LEAFY HULL STERILE1 (WLHS1), which are homologs of Os MADS45 and Os MADS1 in rice (Oryza sativa), respectively. The three wheat homoeologs of WSEP showed similar genomic structures and expression profiles. By contrast, the three homoeologs of WLHS1 showed genetic and epigenetic alterations. The A genome WLHS1 homoeolog (WLHS1-A) had a structural alteration that contained a large novel sequence in place of the K domain sequence. A yeast two-hybrid analysis and a transgenic experiment indicated that the WLHS1-A protein had no apparent function. The B and D genome homoeologs, WLHS1-B and WLHS1-D, respectively, had an intact MADS box gene structure, but WLHS1-B was predominantly silenced by cytosine methylation. Consequently, of the three WLHS1 homoeologs, only WLHS1-D functions in hexaploid wheat. This is a situation where three homoeologs are differentially regulated by genetic and epigenetic mechanisms. 相似文献
98.
The cell biology of the early processes of mammalian embryogenesis, such as germ-layer formation, has been technically challenging to study owing to the size and accessibility of mammalian embryos. Embryonic stem cells, which can generate the three germ layers in vitro, are useful for studying embryogenesis at the cellular level. So, how can the study of embryonic stem cells and their differentiation provide a deeper understanding of the cell biology of early development? 相似文献
99.
Mishra RK Yamagishi T Vasanthi D Ohtsuka C Kondo T 《Genesis (New York, N.Y. : 2000)》2007,45(9):570-576
Temporal colinearity in mouse HoxD is dependent on repressive activity of sequences within the 5' end of the complex. We show that a 5-kb DNA fragment from this region represses transgenes when combined in mouse as well as in Drosophila melanogaster. Moreover, repressive activity in Drosophila depends on some members of the Polycomb-group (PcG) genes, for example, extra sex combs. We also showed direct association of these factors with the repressive fragment, both in transgenic flies and in the context of the native mouse HoxD complex. These results suggest that the global repressive region of the HoxD complex functions in two very different species and that some PcG genes are involved in establishing the early repressive state of the HoxD complex, thus contributing to temporal colinearity. 相似文献
100.
Hydrobiologia - During larval development of the intertidal barnacle Fistulobalanus albicostatus, larvae in the naupliar stages I and II (NI&II) possess a single naupliar eye, and later... 相似文献