全文获取类型
收费全文 | 3894篇 |
免费 | 271篇 |
国内免费 | 5篇 |
出版年
2021年 | 30篇 |
2020年 | 28篇 |
2019年 | 41篇 |
2018年 | 46篇 |
2017年 | 43篇 |
2016年 | 78篇 |
2015年 | 110篇 |
2014年 | 112篇 |
2013年 | 252篇 |
2012年 | 158篇 |
2011年 | 226篇 |
2010年 | 119篇 |
2009年 | 122篇 |
2008年 | 196篇 |
2007年 | 190篇 |
2006年 | 206篇 |
2005年 | 234篇 |
2004年 | 200篇 |
2003年 | 209篇 |
2002年 | 186篇 |
2001年 | 121篇 |
2000年 | 137篇 |
1999年 | 96篇 |
1998年 | 73篇 |
1997年 | 64篇 |
1996年 | 48篇 |
1995年 | 28篇 |
1994年 | 31篇 |
1993年 | 48篇 |
1992年 | 80篇 |
1991年 | 51篇 |
1990年 | 57篇 |
1989年 | 50篇 |
1988年 | 39篇 |
1987年 | 24篇 |
1986年 | 31篇 |
1985年 | 38篇 |
1984年 | 33篇 |
1983年 | 31篇 |
1982年 | 41篇 |
1981年 | 25篇 |
1980年 | 20篇 |
1979年 | 25篇 |
1978年 | 26篇 |
1977年 | 23篇 |
1976年 | 22篇 |
1974年 | 14篇 |
1971年 | 12篇 |
1970年 | 13篇 |
1969年 | 12篇 |
排序方式: 共有4170条查询结果,搜索用时 46 毫秒
1.
Takahiro Watanabe Yohei Narita Masahiro Yoshida Yoshitaka Sato Fumi Goshima Hiroshi Kimura Takayuki Murata 《Journal of virology》2015,89(19):10120-10124
Epstein-Barr virus (EBV) is a gammaherpesvirus, associated with infectious mononucleosis and various types of malignancy. We focused here on the BDLF4 gene of EBV and identified it as a lytic gene, expressed with early kinetics. Viral late gene expression of the BDLF4 knockout strain was severely restricted; this could be restored by an exogenous supply of BDLF4. These results indicate that BDLF4 is important for the EBV lytic replication cycle, especially in late gene expression. 相似文献
2.
3.
Takatoshi Murata Tsutomu Sato Takeshi Kamoda Hiromitsu Moriyama Yasuo Kumazawa Nobuhiro Hanada 《Experimental cell research》2014
Hydrogen sulfide (H2S) is a novel gasotransmitter that plays multiple biological roles in various body systems. In addition to its endogenous production, H2S is produced by bacteria colonizing digestive organs, including the oral cavity. H2S was previously shown to enhance pro-apoptotic effects in cancer cell lines, although the mechanisms involved remain unclear. To properly assess the anti-cancer effects of H2S, however, investigations of apoptotic effects in normal cells are also necessary. The aims of this study were (1) to compare the susceptibility to H2S-induced apoptosis between the oral cancer cell line Ca9-22 and oral keratinocytes that were derived from healthy gingiva, and (2) to identify candidate genes involved in the induction of apoptosis by H2S. The susceptibility to H2S-induced apoptosis in Ca9-22 cells was significantly higher than that in keratinocytes. H2S exposure in Ca9-22 cells, but not keratinocytes, enhanced the expression of pleckstrin homology-like domain, family A, member 1 (PHLDA1), which was identified through a differential display method. In addition, PHLDA1 expression increased during actinomycin D-induced apoptosis in Ca9-22 cells. Knockdown of PHLDA1 expression by small interfering RNA in Ca9-22 cells led to expression of active caspase 3, thus indicating apoptosis induction. The tongue cancer cell line SCC-25, which expresses PHLDA1 at a high level, showed similar effects. Our data indicate that H2S is an anti-cancer compound that may contribute to the low incidence of oral cancer. Furthermore, we demonstrated the role of PHLDA1 as an apoptosis suppressor. 相似文献
4.
Norio Ohashi Masahiro Fukuhara Masahiko Shimada Akira Tamura 《FEMS microbiology letters》1995,125(2-3):299-304
Abstract The 16S rRNA gene sequences of Rickettsia tsutsugamushi and Rickettsia sibirica were determined by PCR and DNA sequencing. Phylogenetic analysis revealed that R. sibirica is positioned in a cluster of the genus Rickettsia with a similarity value of 98.1–99.6%, whereas R. tsutsugamushi is located apart from the cluster with a similarity value of 90.2–90.6%. This evidence suggests that R. tsutsugamushi should be excluded taxonomically from the genus Rickettsia . The phylogenetic classification of six antigenic variants in R. tsutsugamushi moderately reflected their antigenic relationship known in closely and distantly related strains. 相似文献
5.
Expression of the fragile X site fra(X)(q27.3) was studied in thymidine-prototrophic and auxotrophic human-mouse somatic cell hybrids. In these cells, low thymidylate stress, achieved by 5-fluoro-2'-deoxyuridine (FdU) treatment and by limiting the exogenous supply of thymidine (dT), induced fragile X expression. High thymidylate stress, produced by supplying excess amounts of dT, was also effective in inducing fragile X expression, even in a hybrid clone that retained a fragile X chromosome as the only human chromosome; addition of deoxycytidine (dC) completely abolished this effect. In contrast, 5-bromo-2'-deoxyuridine (BrdU) did not induce fragile X expression. Cell-cycle analysis of BrdU-deprived thymidine-auxotrophic hybrid cells indicated that one round of DNA replication under thymidylate stress conditions is sufficient for fragile X expression. Our results suggest that the expression is an intrinsic property of the fragile site itself, which is believed to be composed of replicon clusters with pyrimidine-rich DNA sequence(s). 相似文献
6.
J Murata I Saiki I Azuma N Nishi 《International journal of biological macromolecules》1989,11(2):97-99
A new type of polypeptide containing the repeating sequence of cell attachment site in laminin, poly(Tyr-Ile-Gly-Ser-Arg), was synthesized by the polymerization procedure with diphenylphosphoryl azide (DPPA). We found that this polypeptide inhibited the metastatic formation in the lung of malignant tumour cells far more effectively than pentapeptide. 相似文献
7.
Hoshino Atsushi; Abe Yukihide; Saito Norio; Inagaki Yoshishige; Iida Shigeru 《Plant & cell physiology》1997,38(8):970-974
The Japanese morning glory carrying the recessive mutable speckledallele with the dominant speckled-activator bears colorlessflowers with fine and round colored spots distributed over thecorolla whereas the plant without the speckled-activator producespale yellow flowers. Previous chemical analysis has indicatedthat a mutation in the gene for flavanone 3-hydroxylase (F3H)is a likely candidate for the speckled allele. However, theF3HmRNA without sequence alteration accumulates normally inthe pale yellow flowers, indicating that the speckled alleleis neither the F3H gene nor a regulatory gene acting on theF3H gene expression. (Received April 4, 1997; Accepted June 2, 1997) 相似文献
8.
A putative GDP–GTP exchange factor is required for development of the excretory cell in Caenorhabditis elegans 下载免费PDF全文
Norio Suzuki Matthew Buechner Kiyoji Nishiwaki David H. Hall Hiroyuki Nakanishi Yoshimi Takai Naoki Hisamoto Kunihiro Matsumoto 《EMBO reports》2001,2(6):530-535
The Caenorhabditis elegans excretory cell extends tubular processes, called canals, along the basolateral surface of the epidermis. Mutations in the exc-5 gene cause tubulocystic defects in this canal. Ultrastructural analysis suggests that exc-5 is required for the proper placement of cytoskeletal elements at the apical epithelial surface. exc-5 encodes a protein homologous to guanine nucleotide exchange factors and contains motif architecture similar to that of FGD1, which is responsible for faciogenital dysplasia. exc-5 interacts genetically with mig-2, which encodes Rho GTPase. These results suggest that EXC-5 controls the structural organization of the excretory canal by regulating Rho family GTPase activities. 相似文献
9.
Mio Kawabata Honoka Matsuo Takumi Koito Misaki Murata Tomoko Kubori Hiroki Nagai Mitsuo Tagaya Kohei Arasaki 《PLoS pathogens》2021,17(3)
Legionella pneumophila (L. pneumophila) is a gram-negative bacterium that replicates in a compartment that resembles the host endoplasmic reticulum (ER). To create its replicative niche, L. pneumophila manipulates host membrane traffic and fusion machineries. Bacterial proteins called Legionella effectors are translocated into the host cytosol and play a crucial role in these processes. In an early stage of infection, Legionella subverts ER-derived vesicles (ERDVs) by manipulating GTPase Rab1 to facilitate remodeling of the Legionella-containing vacuole (LCV). Subsequently, the LCV associates with the ER in a mechanism that remains elusive. In this study, we show that L. pneumophila recruits GTPases Rab33B and Rab6A, which regulate vesicle trafficking from the Golgi to the ER, to the LCV to promote the association of LCV with the ER. We found that recruitment of Rab6A to the LCV depends on Rab33B. Legionella effector SidE family proteins, which phosphoribosyl-ubiquitinate Rab33B, were found to be necessary for the recruitment of Rab33B to the LCV. Immunoprecipitation experiments revealed that L. pneumophila facilitates the interaction of Rab6 with ER-resident SNAREs comprising syntaxin 18, p31, and BNIP1, but not tethering factors including NAG, RINT-1, and ZW10, which are normally required for syntaxin 18-mediated fusion of Golgi-derived vesicles with the ER. Our results identified a Rab33B-Rab6A cascade on the LCV and the interaction of Rab6 with ER-resident SNARE proteins for the association of LCV with the ER and disclosed the unidentified physiological role of SidE family proteins. 相似文献
10.
N. Yamada W. Murata Y. Yamaguchi K.-I. Fujita A. Ogita T. Tanaka 《Letters in applied microbiology》2021,72(4):390-398
Amphotericin B (AmB), a typical polyene macrolide antifungal agent, is widely used to treat systemic mycoses. In the present study, we show that the fungicidal activity of AmB was enhanced by benzyl isothiocyanate (BITC), a cruciferous plant-derived compound, in the budding yeast, Saccharomyces cerevisiae. In addition to forming a molecular complex with ergosterol present in fungal cell membranes to form K+-permeable ion channels, AmB has been recognized to mediate vacuolar membrane disruption resulting in lethal effects. BITC showed no effect on AmB-induced plasma membrane permeability; however, it amplified AmB-induced vacuolar membrane disruption in S. cerevisiae. Furthermore, the BITC-enhanced fungicidal effects of AmB significantly decreased cell viability due to the disruption of vacuoles in the pathogenic fungus Candida albicans. The application of the combinatorial antifungal effect of AmB and BITC may aid in dose reduction of AmB in clinical antifungal therapy and consequently decrease side effects in patients. These results also have significant implications for the development of vacuole-targeting chemotherapy against fungal infections. 相似文献