全文获取类型
收费全文 | 2153篇 |
免费 | 117篇 |
专业分类
2270篇 |
出版年
2024年 | 2篇 |
2023年 | 5篇 |
2022年 | 17篇 |
2021年 | 32篇 |
2020年 | 12篇 |
2019年 | 23篇 |
2018年 | 37篇 |
2017年 | 32篇 |
2016年 | 46篇 |
2015年 | 83篇 |
2014年 | 101篇 |
2013年 | 123篇 |
2012年 | 162篇 |
2011年 | 155篇 |
2010年 | 103篇 |
2009年 | 107篇 |
2008年 | 171篇 |
2007年 | 157篇 |
2006年 | 123篇 |
2005年 | 142篇 |
2004年 | 141篇 |
2003年 | 121篇 |
2002年 | 105篇 |
2001年 | 17篇 |
2000年 | 26篇 |
1999年 | 20篇 |
1998年 | 23篇 |
1997年 | 17篇 |
1996年 | 13篇 |
1995年 | 21篇 |
1994年 | 10篇 |
1993年 | 14篇 |
1992年 | 16篇 |
1991年 | 9篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 15篇 |
1985年 | 9篇 |
1984年 | 6篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1974年 | 2篇 |
1954年 | 1篇 |
1953年 | 1篇 |
1952年 | 1篇 |
1951年 | 1篇 |
排序方式: 共有2270条查询结果,搜索用时 15 毫秒
41.
42.
Takashi Seino Shintaro Kawasaki Mariko Shimokawa Hiroki Tamagawa Kohta Toshimitsu Masayuki Fujii Yuki Ohta Mami Matano Kosaku Nanki Kenta Kawasaki Sirirat Takahashi Shinya Sugimoto Eisuke Iwasaki Junichi Takagi Takao Itoi Minoru Kitago Yuko Kitagawa Takanori Kanai Toshiro Sato 《Cell Stem Cell》2018,22(3):454-467.e6
43.
Here, we report the completely annotated genome sequence of Streptococcus pyogenes M1 476 isolated from a patient with streptococcal toxic shock syndrome (STSS) during pregnancy. The genome sequence will provide new insights into the mechanisms underlying STSS. 相似文献
44.
Saito M Kato Y Ito E Fujimoto J Ishikawa K Doi A Kumazawa K Matsui A Takebe S Ishida T Azuma S Mochizuki H Kawamura Y Yanagisawa Y Honma R Imai J Ohbayashi H Goshima N Semba K Watanabe S 《FEBS letters》2012,586(12):1708-1714
Gene amplification is a major genetic alteration in human cancers. Amplicons, amplified genomic regions, are believed to contain "driver" genes responsible for tumorigenesis. However, the significance of co-amplified genes has not been extensively studied. We have established an integrated analysis system of amplicons using retrovirus-mediated gene transfer coupled with a human full-length cDNA set. Applying this system to 17q12-21 amplicon observed in breast cancer, we identified GRB7 as a context-dependent oncogene, which modulates the ERBB2 signaling pathway through enhanced phosphorylation of ERBB2 and Akt. Our work provides an insight into the biological significance of gene amplification in human cancers. 相似文献
45.
Tomohiro Nishimura Shinya Sato Wittaya Tawong Hiroshi Sakanari Keita Uehara Md Mahfuzur Rahman Shah Shoichiro Suda Takeshi Yasumoto Yohsuke Taira Haruo Yamaguchi Masao Adachi 《PloS one》2013,8(4)
Background
The marine epiphytic dinoflagellate genus Gambierdiscus produce toxins that cause ciguatera fish poisoning (CFP): one of the most significant seafood-borne illnesses associated with fish consumption worldwide. So far, occurrences of CFP incidents in Japan have been mainly reported in subtropical areas. A previous phylogeographic study of Japanese Gambierdiscus revealed the existence of two distinct phylotypes: Gambierdiscus sp. type 1 from subtropical and Gambierdiscus sp. type 2 from temperate areas. However, details of the genetic diversity and distribution for Japanese Gambierdiscus are still unclear, because a comprehensive investigation has not been conducted yet.Methods/Principal Finding
A total of 248 strains were examined from samples mainly collected from western and southern coastal areas of Japan during 2006–2011. The SSU rDNA, the LSU rDNA D8–D10 and the ITS region were selected as genetic markers and phylogenetic analyses were conducted. The genetic diversity of Japanese Gambierdiscus was high since five species/phylotypes were detected: including two reported phylotypes (Gambierdiscus sp. type 1 and Gambierdiscus sp. type 2), two species of Gambierdiscus (G. australes and G. cf. yasumotoi) and a hitherto unreported phylotype Gambierdiscus sp. type 3. The distributions of type 3 and G. cf. yasumotoi were restricted to the temperate and the subtropical area, respectively. On the other hand, type 1, type 2 and G. australes occurred from the subtropical to the temperate area, with a tendency that type 1 and G. australes were dominant in the subtropical area, whereas type 2 was dominant in the temperate area. By using mouse bioassay, type 1, type 3 and G. australes exhibited mouse toxicities.Conclusions/Significance
This study revealed a surprising diversity of Japanese Gambierdiscus and the distribution of five species/phylotypes displayed clear geographical patterns in Japanese coastal areas. The SSU rDNA and the LSU rDNA D8–D10 as genetic markers are recommended for further use. 相似文献46.
Calmodulin‐like skin protein protects against spatial learning impairment in a mouse model of Alzheimer disease 下载免费PDF全文
Shinya Kusakari Mikiro Nawa Katsuko Sudo Masaaki Matsuoka 《Journal of neurochemistry》2018,144(2):218-233
47.
Ishii K Kanatsu-Shinohara M Toyokuni S Shinohara T 《Development (Cambridge, England)》2012,139(10):1734-1743
Fibroblast growth factor 2 (FGF2) and glial cell line-derived neurotrophic factor (GDNF) are required to recapitulate spermatogonial stem cell (SSC) self-renewal in vitro. Although studies have revealed the role of the GDNF signaling pathway in SSCs, little is known about how FGF2 is involved. In the present study, we assessed the role of the FGF2 signaling pathway using a mouse germline stem (GS) cell culture system that allows in vitro expansion of SSCs. Adding GDNF or FGF2 induced phosphorylation of MAPK1/3, and adding the MAP2K1 inhibitor PD0325091 reduced GS cell proliferation and MAPK1/3 phosphorylation. Moreover, GS cells transfected with an activated form of Map2k1 not only upregulated Etv5 and Bcl6b gene expression, but also proliferated in an FGF2-independent manner, suggesting that they act downstream of MAP2K1 signaling to drive SSC self-renewal. Although GS cells transfected with Map2k1, Etv5 or Bcl6b showed normal spermatogonial markers, transplanting GS cells expressing Bcl6b into infertile mouse testes resulted in the formation of a germ cell tumor, suggesting that excessive self-renewal signals causes tumorigenic conversion. These results show that FGF2 depends on MAP2K1 signaling to drive SSC self-renewal via upregulation of the Etv5 and Bcl6b genes. 相似文献
48.
Blanpain C Daley GQ Hochedlinger K Passegué E Rossant J Yamanaka S 《Nature reviews. Molecular cell biology》2012,13(7):471-476
The increasing momentum of stem cell research continues, with the better characterization of induced pluripotent stem (iPS) cells, the conversion of differentiated cells into different cell types and the use of pluripotent stem cells to generate whole tissues, among other advances. Here, six experts in the field of stem cell research compare different stem cell models and highlight the importance of pursuing complementary experimental approaches for a better understanding of pluripotency and differentiation and an informed approach to medical applications. 相似文献
49.
Ginting TE Shinya K Kyan Y Makino A Matsumoto N Kaneda S Kawaoka Y 《Journal of virology》2012,86(1):121-127
Oseltamivir-resistant H1N1 influenza viruses emerged in 2007 to 2008 and have subsequently circulated widely. However, prior to 2007 to 2008, viruses possessing the neuraminidase (NA) H274Y mutation, which confers oseltamivir resistance, generally had low growth capability. NA mutations that compensate for the deleterious effect of the NA H274Y mutation have since been identified. Given the importance of the functional balance between hemagglutinin (HA) and NA, we focused on amino acid changes in HA. Reverse genetic analysis showed that a mutation at residue 82, 141, or 189 of the HA protein promotes virus replication in the presence of the NA H274Y mutation. Our findings thus identify HA mutations that contributed to the replacement of the oseltamivir-sensitive viruses of 2007 to 2008. 相似文献
50.
Introns are generally believed to evolve too rapidly and too erratically to be of much use in phylogenetic reconstructions.
Few phylogenetically informative intron sequences are available, however, to ascertain the validity of this supposition. In
the present study the supposition was tested on the example of the mammalian class II major histocompatibility complex (Mhc) genes of the DRB family. Since the Mhc genes evolve under balancing selection and are believed to recombine or rearrange frequently, the evolution of their introns
could be expected to be particularly rapid and subject to scrambling. Sequences of intron 4 and 5 DRB genes were obtained from polymerase chain reaction-amplified fragments of genomic DNA from representatives of six eutherian
orders—Primates, Scandentia, Chiroptera, Dermoptera, Lagomorpha, and Insectivora. Although short stretches of the introns
have indeed proved to be unalignable, the bulk of the intron sequences from all six orders, spanning >85 million years (my)
of evolution, could be aligned and used in a study of the tempo and mode of intron evolution. The analysis has revealed the
Mhc introns to evolve at a rate similar to that of other genes and of synonymous sites of non-Mhc genes. No evidence of homogenization or large-scale scrambling of the intron sequences could be found. The Mhc introns apparently evolve largely by point mutations and insertions/deletions. The phylogenetic signals contained in the
intron sequences could be used to identify Scandentia as the sister group of Primates, to support the existence of the Archonta
superorder, and to confirm the monophyly of the Chiroptera.
Received: 26 October 1998 / Accepted: 21 December 1998 相似文献