全文获取类型
收费全文 | 728篇 |
免费 | 41篇 |
国内免费 | 1篇 |
出版年
2022年 | 7篇 |
2021年 | 8篇 |
2020年 | 6篇 |
2019年 | 12篇 |
2018年 | 16篇 |
2017年 | 15篇 |
2016年 | 18篇 |
2015年 | 30篇 |
2014年 | 38篇 |
2013年 | 52篇 |
2012年 | 72篇 |
2011年 | 65篇 |
2010年 | 42篇 |
2009年 | 28篇 |
2008年 | 48篇 |
2007年 | 42篇 |
2006年 | 34篇 |
2005年 | 41篇 |
2004年 | 27篇 |
2003年 | 22篇 |
2002年 | 35篇 |
2001年 | 6篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 6篇 |
1990年 | 2篇 |
1987年 | 5篇 |
1985年 | 5篇 |
1984年 | 6篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 6篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1970年 | 2篇 |
1968年 | 2篇 |
1967年 | 1篇 |
1966年 | 2篇 |
1961年 | 1篇 |
排序方式: 共有770条查询结果,搜索用时 0 毫秒
51.
52.
Two new acyl sucroses were isolated from the epigeal parts of Petunia nyctaginiflora Juss. (Solanaceae). Their structures were determined to be 2, 3, 4-tri (5-methylhexanoyl)-alpha-D-glucopyranosyl-beta-D-fructofuranoside (2) and 2, 3, 4-tri (6-methylheptanoyl)-alpha-D-glucopyranosyl-beta-D-fructofuranoside (4) on the basis of chemical and spectroscopic evidence. 相似文献
53.
Menthol is a highly valued monoterpene produced by Japanese mint (Mentha arvensis) as a natural product with wide applications in cosmetics, confectionery, flavours, beverages and therapeutics. Selection
of high menthol yielding genotypes is therefore the ultimate objective of all genetic improvement programmes inMentha arvensis. A positive correlation was observed in the present study between menthol content in oils of evaluated genotypes and the
level of tolerance to externally supplied menthol of explants of these genotypes in culture medium. The easy use of this relationship
as a selectable biochemical marker opens the practical applicability of largescalein vitro screening of the germplasm, clones and breeders' material for selection of elite genotypes. 相似文献
54.
Ajit Kumar Shasany Suman P. S. Khanujia Sunita Dhawan Usha Yadav Srikant Sharma Sushil Kumar 《Journal of biosciences》1998,23(5):641-646
Media and incubation conditions have been defined for highly efficient regeneration of shoots from internode explants of slow
and fast growing cultivars ofMentha arvensis. Internodal segments excised from thein vitro raised shoots were inoculated on the MS medium supplemented with combinations of 5 concentrations of l-napthalene acetic
acid (NAA) and 3 concentrations of 6-benzyl amino purine (BAP). The media containing 2 μg ml−1 NAA, 10 Μg ml−1 BAP and 1 μg ml−1 NAA, 5 μg ml−1 BAP proved best for shoot regeneration and growth responses on cv Himalaya and cv Kalka explants, respectively. In 12 weeks
time, on average one explant of cv Himalaya produced about 200 shoots and that of cv Kalka produced about 180 shoots. The
Himalaya explants required higher concentrations of NAA and BAP for high efficiency proliferation as compared to the Kalka
explants. The experiments demonstrated that internodal tissue inMentha arvensis can be induced to obtain direct shoot regenerants with high efficiency. The analysis of the RAPD profiles of 100 regenerated
plantlets each of cv Himalaya and Kalka showed more than 99.9% homogeneity in bands with respect to the parents. 相似文献
55.
56.
Erdenebileg Uyangaa Jin Hyoung Kim Ajit Mahadev Patil Jin Young Choi Seong Bum Kim Seong Kug Eo 《PLoS pathogens》2015,11(11)
Type I interferon (IFN-I)-dependent orchestrated mobilization of innate cells in inflamed tissues is believed to play a critical role in controlling replication and CNS-invasion of herpes simplex virus (HSV). However, the crucial regulators and cell populations that are affected by IFN-I to establish the early environment of innate cells in HSV-infected mucosal tissues are largely unknown. Here, we found that IFN-I signaling promoted the differentiation of CCL2-producing Ly-6Chi monocytes and IFN-γ/granzyme B-producing NK cells, whereas deficiency of IFN-I signaling induced Ly-6Clo monocytes producing CXCL1 and CXCL2. More interestingly, recruitment of Ly-6Chi monocytes preceded that of NK cells with the levels peaked at 24 h post-infection in IFN-I–dependent manner, which was kinetically associated with the CCL2-CCL3 cascade response. Early Ly-6Chi monocyte recruitment was governed by CCL2 produced from hematopoietic stem cell (HSC)-derived leukocytes, whereas NK cell recruitment predominantly depended on CC chemokines produced by resident epithelial cells. Also, IFN-I signaling in HSC-derived leukocytes appeared to suppress Ly-6Ghi neutrophil recruitment to ameliorate immunopathology. Finally, tissue resident CD11bhiF4/80hi macrophages and CD11chiEpCAM+ dendritic cells appeared to produce initial CCL2 for migration-based self-amplification of early infiltrated Ly-6Chi monocytes upon stimulation by IFN-I produced from infected epithelial cells. Ultimately, these results decipher a detailed IFN-I–dependent pathway that establishes orchestrated mobilization of Ly-6Chi monocytes and NK cells through CCL2-CCL3 cascade response of HSC-derived leukocytes and epithelium-resident cells. Therefore, this cascade response of resident–to-hematopoietic–to-resident cells that drives cytokine–to-chemokine–to-cytokine production to recruit orchestrated innate cells is critical for attenuation of HSV replication in inflamed tissues. 相似文献
57.
Ajit G. Thomas Rita Sattler Karen Tendyke Kara A. Loiacono Hans Hansen Vishal Sahni Yutaka Hashizume Camilo Rojas Barbara S. Slusher 《PloS one》2015,10(8)
The cystine-glutamate antiporter (system xc
-) is a Na+-independent amino acid transporter that exchanges extracellular cystine for intracellular glutamate. It is thought to play a critical role in cellular redox processes through regulation of intracellular glutathione synthesis via cystine uptake. In gliomas, system xc
- expression is universally up-regulated while that of glutamate transporters down-regulated, leading to a progressive accumulation of extracellular glutamate and excitotoxic cell death of the surrounding non-tumorous tissue. Additionally, up-regulation of system xc
- in activated microglia has been implicated in the pathogenesis of several neurodegenerative disorders mediated by excess glutamate. Consequently, system xc
- is a new drug target for brain cancer and neuroinflammatory diseases associated with excess extracellular glutamate. Unfortunately no potent and selective small molecule system xc
- inhibitors exist and to our knowledge, no high throughput screening (HTS) assay has been developed to identify new scaffolds for inhibitor design. To develop such an assay, various neuronal and non-neuronal human cells were evaluated as sources of system xc
-. Human glioma cells were chosen based on their high system xc
- activity. Using these cells, [14C]-cystine uptake and cystine-induced glutamate release assays were characterized and optimized with respect to cystine and protein concentrations and time of incubation. A pilot screen of the LOPAC/NINDS libraries using glutamate release demonstrated that the logistics of the assay were in place but unfortunately, did not yield meaningful pharmacophores. A larger, HTS campaign using the 384-well cystine-induced glutamate release as primary assay and the 96-well 14C-cystine uptake as confirmatory assay is currently underway. Unexpectedly, we observed that the rate of cystine uptake was significantly faster than the rate of glutamate release in human glioma cells. This was in contrast to the same rates of cystine uptake and glutamate release previously reported in normal human fibroblast cells. 相似文献
58.
Deepak Raina Praveen Agarwal James Lee Ajit Bharti C. James McKnight Pankaj Sharma Surender Kharbanda Donald Kufe 《PloS one》2015,10(8)
Mucin 1 (MUC1) is a heterodimeric protein that is aberrantly expressed in diverse human carcinomas and certain hematologic malignancies. The oncogenic MUC1 transmembrane C-terminal subunit (MUC1-C) functions in part by transducing growth and survival signals from cell surface receptors. However, little is known about the structure of the MUC1-C cytoplasmic domain as a potential drug target. Using methods for structural predictions, our results indicate that a highly conserved CQCRRK sequence, which is adjacent to the cell membrane, forms a small pocket that exposes the two cysteine residues for forming disulfide bonds. By contrast, the remainder of the MUC1-C cytoplasmic domain has no apparent structure, consistent with an intrinsically disordered protein. Our studies thus focused on targeting the MUC1 CQCRRK region. The results show that L- and D-amino acid CQCRRK-containing peptides bind directly to the CQC motif. We further show that the D-amino acid peptide, designated GO-203, blocks homodimerization of the MUC1-C cytoplasmic domain in vitro and in transfected cells. Moreover, GO-203 binds directly to endogenous MUC1-C in breast and lung cancer cells. Colocalization studies further demonstrate that GO-203 predominantly binds to MUC1-C at the cell membrane. These findings support the further development of agents that target the MUC1-C cytoplasmic domain CQC motif and thereby MUC1-C function in cancer cells. 相似文献
59.
Ajit Kumar Ngangbam Abdul Baten Daniel L. E. Waters Steve Whalan Kirsten Benkendorff 《PloS one》2015,10(10)
Dicathais orbita is a marine mollusc recognised for the production of anticancer compounds that are precursors to Tyrian purple. This study aimed to assess the diversity and identity of bacteria associated with the Tyrian purple producing hypobranchial gland, in comparison with foot tissue, using a high-throughput sequencing approach. Taxonomic and phylogenetic analysis of variable region V1-V3 of 16S rRNA bacterial gene amplicons in QIIME and MEGAN were carried out. This analysis revealed a highly diverse bacterial assemblage associated with the hypobranchial gland and foot tissues of D. orbita. The dominant bacterial phylum in the 16S rRNA bacterial profiling data set was Proteobacteria followed by Bacteroidetes, Tenericutes and Spirochaetes. In comparison to the foot, the hypobranchial gland had significantly lower bacterial diversity and a different community composition, based on taxonomic assignment at the genus level. A higher abundance of indole producing Vibrio spp. and the presence of bacteria with brominating capabilities in the hypobranchial gland suggest bacteria have a potential role in biosynthesis of Tyrian purple in D. orbita. 相似文献
60.
Ajit G. Thomas Cliona M. O’Driscoll Joseph Bressler Walter E. Kaufmann Camilo J. Rojas Barbara S. Slusher 《Biochemical and biophysical research communications》2014
Glutaminase plays a critical role in the generation of glutamate, a key excitatory neurotransmitter in the CNS. Excess glutamate release from activated macrophages and microglia correlates with upregulated glutaminase suggesting a pathogenic role for glutaminase. Both glutaminase siRNA and small molecule inhibitors have been shown to decrease excess glutamate and provide neuroprotection in multiple models of disease, including HIV-associated dementia (HAD), multiple sclerosis and ischemia. Consequently, inhibition of glutaminase could be of interest for treatment of these diseases. Bis-2-(5-phenylacetimido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) and 6-diazo-5-oxo-l-norleucine (DON), two most commonly used glutaminase inhibitors, are either poorly soluble or non-specific. Recently, several new BPTES analogs with improved physicochemical properties were reported. To evaluate these new inhibitors, we established a cell-based microglial activation assay measuring glutamate release. Microglia-mediated glutamate levels were significantly augmented by tumor necrosis factor (TNF)-α, phorbol 12-myristate 13-acetate (PMA) and Toll-like receptor (TLR) ligands coincident with increased glutaminase activity. While several potent glutaminase inhibitors abrogated the increase in glutamate, a structurally related analog devoid of glutaminase activity was unable to block the increase. In the absence of glutamine, glutamate levels were significantly attenuated. These data suggest that the in vitro microglia assay may be a useful tool in developing glutaminase inhibitors of therapeutic interest. 相似文献