全文获取类型
收费全文 | 167篇 |
免费 | 16篇 |
专业分类
183篇 |
出版年
2022年 | 2篇 |
2021年 | 7篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 5篇 |
2015年 | 10篇 |
2014年 | 10篇 |
2013年 | 15篇 |
2012年 | 13篇 |
2011年 | 12篇 |
2010年 | 6篇 |
2009年 | 9篇 |
2008年 | 9篇 |
2007年 | 12篇 |
2006年 | 9篇 |
2005年 | 4篇 |
2004年 | 3篇 |
2003年 | 4篇 |
2002年 | 2篇 |
2001年 | 2篇 |
2000年 | 6篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1976年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有183条查询结果,搜索用时 0 毫秒
81.
82.
Om Prakash Narayan Nidhi Kumari Poonam Bhargava Hema Rajaram Lal Chand Rai 《Functional & integrative genomics》2016,16(1):67-78
DNA-binding proteins (Dps) induced during starvation play an important role in gene regulation and maintaining homeostasis in bacteria. The nitrogen-fixing cyanobacterium, Anabaena PCC7120, has four genes annotated as coding for Dps; however, the information on their physiological roles is limiting. One of the genes coding for Dps, ‘all3940’ was found to be induced under different abiotic stresses in Anabaena and upon overexpression enhanced the tolerance of Anabaena to a multitude of stresses, which included salinity, heat, heavy metals, pesticide, and nutrient starvation. On the other hand, mutation in the gene resulted in decreased growth of Anabaena. The modulation in the levels of All3940 in Anabaena, achieved either by overexpression of the protein or mutation of the gene, resulted in changes in the proteome, which correlated well with the physiological changes observed. Proteins required for varied physiological activities, such as photosynthesis, carbon-metabolism, oxidative stress alleviation, exhibited change in protein profile upon modulation of All3940 levels in Anabaena. This suggested a direct or an indirect effect of All3940 on the expression of the above stress-responsive proteins, thereby enhancing tolerance in Anabaena PCC7120. Thus, All3940, though categorized as a Dps, is possibly a general stress protein having a global role in regulating tolerance to multitude of stresses in Anabaena. 相似文献
83.
Megha Rajaram Jianping Zhang Tim Wang Jinyu Li Cem Kuscu Huan Qi Mamoru Kato Vladimir Grubor Robert J. Weil Aslaug Helland Anne-Lise Borrenson-Dale Kathleen R. Cho Douglas A. Levine Alan N. Houghton Jedd D. Wolchok Lois Myeroff Sanford D. Markowitz Scott W. Lowe Michael Zhang Alex Krasnitz Robert Lucito David Mu R. Scott Powers 《PloS one》2013,8(6)
One of the key questions about genomic alterations in cancer is whether they are functional in the sense of contributing to the selective advantage of tumor cells. The frequency with which an alteration occurs might reflect its ability to increase cancer cell growth, or alternatively, enhanced instability of a locus may increase the frequency with which it is found to be aberrant in tumors, regardless of oncogenic impact. Here we’ve addressed this on a genome-wide scale for cancer-associated focal deletions, which are known to pinpoint both tumor suppressor genes (tumor suppressors) and unstable loci. Based on DNA copy number analysis of over one-thousand human cancers representing ten different tumor types, we observed five loci with focal deletion frequencies above 5%, including the A2BP1 gene at 16p13.3 and the MACROD2 gene at 20p12.1. However, neither RNA expression nor functional studies support a tumor suppressor role for either gene. Further analyses suggest instead that these are sites of increased genomic instability and that they resemble common fragile sites (CFS). Genome-wide analysis revealed properties of CFS-like recurrent deletions that distinguish them from deletions affecting tumor suppressor genes, including their isolation at specific loci away from other genomic deletion sites, a considerably smaller deletion size, and dispersal throughout the affected locus rather than assembly at a common site of overlap. Additionally, CFS-like deletions have less impact on gene expression and are enriched in cell lines compared to primary tumors. We show that loci affected by CFS-like deletions are often distinct from known common fragile sites. Indeed, we find that each tumor tissue type has its own spectrum of CFS-like deletions, and that colon cancers have many more CFS-like deletions than other tumor types. We present simple rules that can pinpoint focal deletions that are not CFS-like and more likely to affect functional tumor suppressors. 相似文献
84.
A family knockout of all four Drosophila metallothioneins reveals a central role in copper homeostasis and detoxification 下载免费PDF全文
85.
Thalidomide attenuates nitric oxide mediated angiogenesis by blocking migration of endothelial cells
KP Tamilarasan Gopi Krishna Kolluru Megha Rajaram M Indhumathy R Saranya Suvro Chatterjee 《BMC cell biology》2006,7(1):17-13
Background
Thalidomide is an immunomodulatory agent, which arrests angiogenesis. The mechanism of anti-angiogenic activity of thalidomide is not fully understood. As nitric oxide is involved in angiogenesis, we speculate a cross-talk between thalidomide and nitric oxide signaling pathway to define angiogenesis. The aim of present study is to understand the mechanistic aspects of thalidomide-mediated attenuation of angiogenesis induced by nitric oxide at the cellular level. 相似文献86.
87.
Kim C. Mansky Eric D. Jensen Julia Davidova Masato Yamamoto Rajaram Gopalakrishnan 《The Journal of biological chemistry》2013,288(14):9826-9834
Although PKD is broadly expressed and involved in numerous cellular processes, its function in osteoclasts has not been previously reported. In this study, we found that PKD2 is the main PKD isoform expressed in osteoclastic cells. PKD phosphorylation, indicative of the activated state, increased after 2–3 days of treatment of bone marrow macrophages with M-CSF and RANKL, corresponding to the onset of preosteoclast fusion. RNAi against PKD2 and treatment with the PKD inhibitor CID755673 showed that PKD activity is dispensable for induction of bone marrow macrophages into tartrate-resistant acid phosphatase-positive preosteoclasts in culture but is required for the transition from mononucleated preosteoclasts to multinucleated osteoclasts. Loss of PKD activity reduced expression of DC-STAMP in RANKL-stimulated cultures. Overexpression of DC-STAMP was sufficient to rescue treatment with CID755673 and restore fusion into multinucleated osteoclasts. From these data, we conclude that PKD activity promotes differentiation of osteoclast progenitors through increased expression of DC-STAMP. 相似文献
88.
Singanaboina Rajaram Udugu Ramulu Dasari Ramesh Dudem Srikanth Papri Bhattacharya Peddikotla Prabhakar Shasi V. Kalivendi Katragadda Suresh Babu Yenamandra Venkateswarlu Suryakiran Navath 《Bioorganic & medicinal chemistry letters》2013,23(23):6234-6238
The chemical investigation of soft coral Sinularia kavarattiensis is described. It yielded furano-sesquiterpene carboxylic acids 1 and 2 and their methyl esters 3 and 4. Semi-synthesis of furano-sesquiterpene carboxylic acid 1 gave amide derivatives 5–12. Structures of all the compounds were established by IR, NMR and mass spectral analysis. Interestingly all compounds are selectively potent on leukemia cell line. All these compounds were screened for cytotoxic activity against five human cancer cell lines (leukemia, prostate, lung, breast and cervix). Among these compounds 9 and 10 showed promising activity against leukemia and prostate cancer cell lines. 相似文献
89.
Rajaram Shyam Kumar Innasi Muthu Ganesh Moorthy Rajoo Baskar 《Preparative biochemistry & biotechnology》2013,43(7):668-681
In this study, a hybrid system of response surface methodology followed by genetic algorithm has been adopted to optimize the production medium for L-glutamic acid fermentation with mixed cultures of Corynebacterium glutamicum and Pseudomonas reptilovora. The optimal combination of media components for maximal production of L-glutamic acid was found to be 49.99 g L?1 of glucose, 10 g L?1 of urea, 18.06% (v/v) of salt solution, and 4.99% (v/v) of inoculum size. The experimental glutamic acid yield at optimum condition was 19.69 g L?1, which coincided well to the value predicted by the model (19.61 g L?1). Using this methodology, a nonlinear regression model was developed for the glutamic acid production. The model was validated statistically and the determination coefficient (R 2) was found to be 0.99. 相似文献
90.
Torrelles JB Sieling PA Arcos J Knaup R Bartling C Rajaram MV Stenger S Modlin RL Schlesinger LS 《The Journal of biological chemistry》2011,286(41):35438-35446
Mannosylated molecules on the Mycobacterium tuberculosis surface are important determinants in the immunopathogenesis of tuberculosis. To date, much attention has been paid to mannose-capped lipoarabinomannan, which mediates phagocytosis and intracellular trafficking of M. tuberculosis by engaging the macrophage mannose receptor and subsequently binds to intracellular CD1b molecules for presentation to T cells. Another important mannosylated lipoglycan on the M. tuberculosis surface is lipomannan (LM). Comparative structural detail of the LMs from virulent and avirulent strains is limited as is knowledge regarding their differential capacity to be recognized by the adaptive immune response. Here, we purified LM from the avirulent M. smegmatis and the virulent M. tuberculosis H(37)R(v), performed a comparative structural biochemical analysis, and addressed their ability to stimulate CD1b-restricted T cell clones. We found that M. tuberculosis H(37)R(v) produces a large neutral LM (TB-LM); in contrast, M. smegmatis produces a smaller linear acidic LM (SmegLM) with a high succinate content. Correspondingly, TB-LM was not as efficiently presented to CD1b-restricted T cells as SmegLM. Thus, here we correlate the structure-function relationships for LMs with CD1b-restricted T cell responses and provide evidence that the structural features of TB-LM contribute to its diminished T cell responsiveness. 相似文献