全文获取类型
收费全文 | 596篇 |
免费 | 39篇 |
国内免费 | 3篇 |
出版年
2022年 | 5篇 |
2021年 | 8篇 |
2020年 | 8篇 |
2019年 | 6篇 |
2018年 | 8篇 |
2017年 | 9篇 |
2016年 | 17篇 |
2015年 | 22篇 |
2014年 | 23篇 |
2013年 | 40篇 |
2012年 | 40篇 |
2011年 | 37篇 |
2010年 | 24篇 |
2009年 | 29篇 |
2008年 | 32篇 |
2007年 | 41篇 |
2006年 | 44篇 |
2005年 | 47篇 |
2004年 | 34篇 |
2003年 | 33篇 |
2002年 | 38篇 |
2001年 | 4篇 |
2000年 | 7篇 |
1999年 | 8篇 |
1998年 | 4篇 |
1997年 | 8篇 |
1996年 | 3篇 |
1995年 | 6篇 |
1994年 | 3篇 |
1993年 | 7篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1989年 | 6篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 8篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1975年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有638条查询结果,搜索用时 509 毫秒
41.
Madoka Koyanagi Julie A Kerns Linda Chung Yan Zhang Scott Brown Tudor Moldoveanu Harmit S Malik Mark Bix 《BMC evolutionary biology》2010,10(1):223
Background
Interleukin-4 (IL4) is a secreted immunoregulatory cytokine critically involved in host protection from parasitic helminths [1]. Reasoning that helminths may have evolved mechanisms to antagonize IL4 to maximize their dispersal, we explored mammalian IL4 evolution. 相似文献42.
Follow-up testing of rodent carcinogens not positive in the standard genotoxicity testing battery: IWGT workgroup report 总被引:1,自引:0,他引:1
Kasper P Uno Y Mauthe R Asano N Douglas G Matthews E Moore M Mueller L Nakajima M Singer T Speit G;IWGT Workgroup 《Mutation research》2007,627(1):106-116
At the Plymouth Third International Workshop on Genotoxicity Testing in June 2002, a new expert group started a working process to provide guidance on a common strategy for genotoxicity testing beyond the current standard battery. The group identified amongst others "Follow-up testing of tumorigenic agents not positive in the standard genotoxicity test battery" as one subject for further consideration [L. Müller, D. Blakey, K.L. Dearfield, S. Galloway, P. Guzzie, M. Hayashi, P. Kasper, D. Kirkland, J.T. MacGregor, J.M. Parry, L. Schechtman, A. Smith, N. Tanaka, D. Tweats, H. Yamasaki, Strategy for genotoxicity testing and stratification of genotoxicity test results-report on initial activities of the IWGT Expert Group, Mutat. Res. 540 (2003) 177-181]. A workgroup devoted to this topic was formed and met on September 9-10, 2005, in San Francisco. This workgroup was devoted to the discussion of when it would be appropriate to conduct additional genetic toxicology studies, as well as what type of studies, if the initial standard battery of tests was negative, but tumor formation was observed in the rodent carcinogenicity assessment. The important role of the standard genetic toxicology testing to determine the mode of action (MOA) for carcinogenesis (genotoxic versus non-genotoxic) was discussed, but the limitations of the standard testing were also reviewed. The workgroup also acknowledged that the entire toxicological profile (e.g. structure-activity relationships, the nature of the tumor finding and metabolic profiles) of a compound needed to be taken into consideration before the conduct of any additional testing. As part of the meeting, case studies were discussed to understand the practical application of additional testing as well as to form a decision tree. Finally, suitable additional genetic toxicology assays to help determine the carcinogenic MOA or establish a weight of evidence (WOE) argument were discussed and formulated into a decision tree. 相似文献
43.
44.
Niba Emma Tabe Eko; Naka Yoshiaki; Nagase Megumi; Mori Hirotada; Kitakawa Madoka 《DNA research》2007,14(6):237-246
Biofilm forming cells are distinctive from the well-investigatedplanktonic cells and exhibit a different type of gene expression.Several new Escherichia coli genes related to biofilm formationhave recently been identified through genomic approaches suchas DNA microarray analysis. However, many others involved inthis process might have escaped detection due to poor expression,regulatory mechanism, or genetic backgrounds. Here, we screeneda collection of single-gene deletion mutants of E. coli namedKeio collection to identify genes required forbiofilm formation. Of the 3985 mutants of non-essential genesin the collection thus examined, 110 showed a reduction in biofilmformation nine of which have not been well characterized yet.Systematic and quantitative analysis revealed the involvementof genes of various functions and reinforced the importancein biofilm formation of the genes for cell surface structuresand cell membrane. Characterization of the nine mutants of function-unknowngenes indicated that some of them, such as yfgA that geneticallyinteracts with a periplasmic chaperone gene surA together withyciB and yciM, might be required for the integrity of outermembrane. 相似文献
45.
Mizuha Y Yamamoto H Sato T Tsuji M Masuda M Uchida M Sakai K Taketani Y Yasutomo K Sasaki H Takeda E 《BioFactors (Oxford, England)》2007,30(2):105-116
It has been reported that Cordyceps sinensis, a traditional Chinese medicine, has various pharmacological effects. The aim of this study was to clarify the effect of water extract of Cordyceps sinensis (WECS) on osteoclast differentiation in vitro. In mouse bone marrow cells and monocyte/macrophage cell line RAW264.7, WECS dose-dependently inhibited the receptor activator of nuclear factor kappa B (NF-kappaB) ligand (RANKL)-induced osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) staining. In fact, cytotoxic effect was not observed in the RAW264.7 cells treated with WECS. Moreover, the mRNA expression of osteoclast related genes (calcitonin receptor, cathepsin K, matrix metalloprotease 9 and nuclear factor of activated T cells c1) was also inhibited by WECS. Investigation of inhibitory mechanism by using electrophoretic mobility shift assay (EMSA) and Western blot analysis revealed that WECS inhibited the activation of NF-kappaB through the prevention of IkappaBalpha phosphorylation. In conclusion, the present results demonstrate for the first time that WECS is a potent inhibitor of the RANKL-induced osteoclast differentiation through a mechanism involving the NF-kappaB pathway. 相似文献
46.
On-chip identification and interaction analysis of gel-resolved proteins using a diamond-like carbon-coated plate 总被引:2,自引:0,他引:2
Iwafune Y Tan JZ Ino Y Okayama A Ishigaki Y Saito K Suzuki N Arima M Oba M Kamei S Tanga M Okada T Hirano H 《Journal of proteome research》2007,6(6):2315-2322
We developed a novel protein chip made of a diamond-like, carbon-coated stainless steel plate (DLC plate), the surface of which is chemically modified with N-hydroxysuccinimide ester. To produce a high-density protein chip using the DLC plate, proteins separated by SDS gel electrophoresis or two-dimensional electrophoresis were electroblotted onto the DLC plate and immobilized covalently. A high blotting efficiency (25-70%) for transferring proteins from the gels onto the DLC plates was achieved by improvement of the electrophoresis device and electroblotting techniques. With the use of the DLC plate, we developed novel techniques to identify proteins immobilized on the chip and to detect protein-protein interactions on the chip by mass spectrometric analysis. We also developed a technique to identify post-translationally modified proteins, such as glycoproteins, on the protein chip. 相似文献
47.
Dysregulation of the Bmi‐1/p16Ink4a pathway provokes an aging‐associated decline of submandibular gland function
下载免费PDF全文
![点击此处可从《Aging cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Kimi Yamakoshi Satoshi Katano Mayu Iida Hiromi Kimura Atsushi Okuma Madoka Ikemoto‐Uezumi Naoko Ohtani Eiji Hara Mitsuo Maruyama 《Aging cell》2015,14(4):616-624
Bmi‐1 prevents stem cell aging, at least partly, by blocking expression of the cyclin‐dependent kinase inhibitor p16Ink4a. Therefore, dysregulation of the Bmi‐1/p16Ink4a pathway is considered key to the loss of tissue homeostasis and development of associated degenerative diseases during aging. However, because Bmi‐1 knockout (KO) mice die within 20 weeks after birth, it is difficult to determine exactly where and when dysregulation of the Bmi‐1/p16Ink4a pathway occurs during aging in vivo. Using real‐time in vivo imaging of p16Ink4a expression in Bmi‐1‐KO mice, we uncovered a novel function of the Bmi‐1/p16Ink4a pathway in controlling homeostasis of the submandibular glands (SMGs), which secrete saliva into the oral cavity. This pathway is dysregulated during aging in vivo, leading to induction of p16Ink4a expression and subsequent declined SMG function. These findings will advance our understanding of the molecular mechanisms underlying the aging‐related decline of SMG function and associated salivary gland hypofunction, which is particularly problematic among the elderly. 相似文献
48.
49.
50.
Teitz T Stanke JJ Federico S Bradley CL Brennan R Zhang J Johnson MD Sedlacik J Inoue M Zhang ZM Frase S Rehg JE Hillenbrand CM Finkelstein D Calabrese C Dyer MA Lahti JM 《PloS one》2011,6(4):e19133