全文获取类型
收费全文 | 7865篇 |
免费 | 504篇 |
国内免费 | 12篇 |
专业分类
8381篇 |
出版年
2023年 | 22篇 |
2022年 | 93篇 |
2021年 | 151篇 |
2020年 | 92篇 |
2019年 | 113篇 |
2018年 | 166篇 |
2017年 | 154篇 |
2016年 | 275篇 |
2015年 | 403篇 |
2014年 | 533篇 |
2013年 | 555篇 |
2012年 | 655篇 |
2011年 | 603篇 |
2010年 | 344篇 |
2009年 | 334篇 |
2008年 | 472篇 |
2007年 | 460篇 |
2006年 | 434篇 |
2005年 | 388篇 |
2004年 | 367篇 |
2003年 | 317篇 |
2002年 | 271篇 |
2001年 | 194篇 |
2000年 | 173篇 |
1999年 | 121篇 |
1998年 | 53篇 |
1997年 | 41篇 |
1996年 | 39篇 |
1995年 | 49篇 |
1994年 | 28篇 |
1993年 | 18篇 |
1992年 | 55篇 |
1991年 | 30篇 |
1990年 | 39篇 |
1989年 | 36篇 |
1988年 | 31篇 |
1987年 | 23篇 |
1986年 | 19篇 |
1985年 | 26篇 |
1984年 | 23篇 |
1983年 | 15篇 |
1982年 | 18篇 |
1981年 | 10篇 |
1979年 | 18篇 |
1978年 | 15篇 |
1976年 | 9篇 |
1975年 | 8篇 |
1974年 | 14篇 |
1973年 | 13篇 |
1972年 | 8篇 |
排序方式: 共有8381条查询结果,搜索用时 0 毫秒
101.
Back Kyoungwhan; He Shuilin; Kim Kil Ung; Shin Dong Hyun 《Plant & cell physiology》1998,39(9):899-904
Sesquiterpene cyclase, a branch point enzyme in the generalisoprenoid pathway for the synthesis of phytoalexin capsidiol,was induced in detached leaves of Capsicum annuum (pepper) byUV treatment. The inducibility of cyclase enzyme activitiesparalleled the absolute amount of cyclase protein(s) of pepperimmunodetected by monoclonal antibodies raised against tobaccosesquiterpene cyclase. A cDNA library was constructed with poly(A)+RNA isolated from 24 h UV-challenged leaves of pepper. A cDNAclone for sesquiterpene cyclase in pepper was isolated by usinga tobacco 5-epi aristolochene synthase gene as a hetero-logousprobe. The predicted protein encoded by this cDNA was comprisedof 559 amino acids and had a relative molecular mass of 65,095.The primary structural information from the cDNA clone revealedthat it shared 77%, 72% and 49% identity with 5-epi aristolochene,vetispiradiene, and cadinene synthase, respectively. The enzymaticproduct catalyzed by the cDNA clone in bacteria was identifiedas 5-epi aristolochene, as judged by argentation TLC. RNA blothybridization demonstrated the induction of an mRNA consistentwith the induction of cyclase enzyme activity in UV-treatedpepper. (Received March 2, 1998; Accepted June 15, 1998) 相似文献
102.
Yuki Hatanaka Natsumi Shimizu Satoshi Nishikawa Mikiko Tokoro Seung-Wook Shin Takuji Nishihara Tomoko Amano Masayuki Anzai Hiromi Kato Tasuku Mitani Yoshihiko Hosoi Satoshi Kishigami Kazuya Matsumoto 《PloS one》2013,8(4)
After fertilization, the sperm and oocyte genomes undergo extensive epigenetic reprogramming to form a totipotent zygote. The dynamic epigenetic changes during early embryo development primarily involve DNA methylation and demethylation. We have previously identified Gse (gonad-specific expression gene) to be expressed specifically in germ cells and early embryos. Its encoded protein GSE is predominantly localized in the nuclei of cells from the zygote to blastocyst stages, suggesting possible roles in the epigenetic changes occurring during early embryo development. Here, we report the involvement of GSE in epigenetic reprogramming of the paternal genome during mouse zygote development. Preferential binding of GSE to the paternal chromatin was observed from pronuclear stage 2 (PN2) onward. A knockdown of GSE by antisense RNA in oocytes produced no apparent effect on the first and second cell cycles in preimplantation embryos, but caused a significant reduction in the loss of 5-methylcytosine (5mC) and the accumulation of 5-hydroxymethylcytosine (5hmC) in the paternal pronucleus. Furthermore, DNA methylation levels in CpG sites of LINE1 transposable elements, Lemd1, Nanog and the upstream regulatory region of the Oct4 (also known as Pou5f1) gene were clearly increased in GSE-knockdown zygotes at mid-pronuclear stages (PN3-4), but the imprinted H19-differential methylated region was not affected. Importantly, DNA immunoprecipitation of 5mC and 5hmC also indicates that knockdown of GSE in zygotes resulted in a significant reduction of the conversion of 5mC to 5hmC on LINE1. Therefore, our results suggest an important role of maternal GSE for mediating active DNA demethylation in the zygote. 相似文献
103.
Gretchen Meinke Paul J. Phelan Radha Kalekar Jong Shin Jacques Archambault Andrew Bohm Peter A. Bullock 《PLoS pathogens》2014,10(2)
JC virus is a member of the Polyomavirus family of DNA tumor viruses and the causative agent of progressive multifocal leukoencephalopathy (PML). PML is a disease that occurs primarily in people who are immunocompromised and is usually fatal. As with other Polyomavirus family members, the replication of JC virus (JCV) DNA is dependent upon the virally encoded protein T-antigen. To further our understanding of JCV replication, we have determined the crystal structure of the origin-binding domain (OBD) of JCV T-antigen. This structure provides the first molecular understanding of JCV T-ag replication functions; for example, it suggests how the JCV T-ag OBD site-specifically binds to the major groove of GAGGC sequences in the origin. Furthermore, these studies suggest how the JCV OBDs interact during subsequent oligomerization events. We also report that the OBD contains a novel “pocket”; which sequesters the A1 & B2 loops of neighboring molecules. Mutagenesis of a residue in the pocket associated with the JCV T-ag OBD interfered with viral replication. Finally, we report that relative to the SV40 OBD, the surface of the JCV OBD contains one hemisphere that is highly conserved and one that is highly variable. 相似文献
104.
Na Na Kim Hyun Suk Shin Young Jae Choi Yuzo Yamamoto Kosuke Fukaya Hiroshi Ueda 《Marine and Freshwater Behaviour and Physiology》2013,45(6):397-410
Migrating fish such as salmonids are affected by external environmental factors and salinity changes are particularly important, influencing spawning migration. The aim of this study was to test whether changes in salinity would affect the expression of the hypothalamic-pituitary-gonadal (HPG) axis hormones (gonadotropin-releasing hormones (GnRHs) [salmon GnRH and chicken GnRH-II], GnRH receptors [GnRHR1 and GnRHR5], and mRNA of the gonadotropin hormone [GTH] subunits [GTHα, follicle stimulating hormone β, and luteinizing hormone β]) in chum salmon (Oncorhynchus keta). Fish were progressively transferred from seawater (SW) through 50% SW to freshwater (FW), and the relationship between the osmoregulatory hormone prolactin (PRL) and sexual maturation was determined. The expression and activity of HPG hormones and their receptors, and levels of estradiol-17β and PRL increased after fish were transferred to FW, demonstrating that changes in salinity stimulate the HPG axis and PRL production in migrating chum salmon. These findings reveal details about the role of the endocrine system in maintaining homeostasis and stimulating sexual maturation and reproduction in response to salinity changes in this species. 相似文献
105.
Hyung Woo Kim Geun Woo Ryu Cheol Ho Park Ea Wha Kang Jung Tak Park Seung Hyeok Han Tae-Hyun Yoo Sug Kyun Shin Shin-Wook Kang Kyu Hun Choi Dae Suk Han Tae Ik Chang 《PloS one》2015,10(6)
Background and Aim
Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients on peritoneal dialysis (PD). Hyponatremia was recently shown to be a modifiable factor that is strongly associated with increased mortality in PD patients. However, the clinical impact of hyponatremia on CV outcomes in these patients is unclear.Methods
To determine whether a low serum sodium level predicts the development of CV disease, we carried out a prospective observational study of 441 incident patients who started PD between January 2000 and December 2005. Time-averaged serum sodium (TA-Na) levels were determined to investigate the ability of hyponatremia to predict newly developed CV events in these patients.Results
During a mean follow-up of 43.2 months, 106 (24.0%) patients developed new CV events. The cumulative incidence of new-onset CV events after the initiation of PD was significantly higher in patients with TA-Na levels ≤ 138 mEq/L than in those with a TA-Na > 138 mEq/L. After adjustment for multiple potentially confounding covariates, an increase in TA-Na level was found to be associated with a significantly lower risk of CV events (subdistribution hazard ratio per 1 mEq/L increase, 0.90; 95% confidence interval, 0.83–0.96; p = 0.003). Patients with a TA-Na ≤ 138 mEq/L had a 2.31-fold higher risk of suffering a CV event.Conclusions
These results provide evidence of a clear association between low serum sodium and new-onset CV events after dialysis initiation in PD patients. Whether the correction of hyponatremia for this indication provides additional protection for the development of CV disease in these patients remains to be addressed in interventional studies. 相似文献106.
Liquid‐like Ionic Conduction in Solid Lithium and Sodium Monocarba‐closo‐decaborates near or at Room Temperature 下载免费PDF全文
107.
Characterization of microbial communities using single-strand conformation polymorphism (SSCP) was compared with that using denaturing gradient gel electrophoresis (DGGE). This comparison was based on the V3-4 region (Escherichia coli positions: 341-806) of 16S rRNA gene of bacterial or archaeal communities obtained from a methanogenic bioreactor. Significant differences in the bacterial banding profiles were observed while attempting to detect the diversity of the community and its succession during the reactor operation. The SSCP produced a number of sharp bands and differentiated the bacterial community structures to which the DGGE gave an identical pattern. On the other hand, the SSCP and DGGE provided similar succession patterns for archaeal community. 相似文献
108.
109.
Muraoka S Shima F Araki M Inoue T Yoshimoto A Ijiri Y Seki N Tamura A Kumasaka T Yamamoto M Kataoka T 《FEBS letters》2012,586(12):1715-1718
GTP-bound Ras adopts two interconverting conformations, "inactive" state 1 and "active" state 2. However, the tertiary structure of wild-type (WT) state 1 remains unsolved. Here we solve the state 1 crystal structures of H-Ras WT together with its oncogenic G12V and Q61L mutants. They assume open structures characterized by impaired interactions of both Thr-35 in switch I and Gly-60 in switch II with the γ-phosphate of GTP and possess two surface pockets of mutually different shapes unseen in state 2, a potential target for selective inhibitor development. Furthermore, they provide a structural basis for the low GTPase activity of state 1. 相似文献
110.
Sung Won Lee Hyun Jung Park Seo Hyun Kim Sooyong Shin Kyung Hee Kim Sang Jae Park 《Animal cells and systems.》2019,23(3):184-191
We recently demonstrated that the polysaccharide component of the Korean medicinal herb Angelica gigas (immuno-stimulatory fraction of A. gigas; ISAg) induces anticancer effects in mice by activating natural killer (NK) and natural killer T (NKT) cells. However, it is unclear whether the use of ISAg in vivo can affect the differentiation of conventional T cells. Here, we investigated the effects of ISAg on the activation of conventional CD4+ and CD8+ T cells. We found that the administration of ISAg induced the polarization of CD4+ T cells toward the acquisition of the Th1 phenotype in vivo. Additionally, in mice treated with ISAg, CD8+ T cells produced more IFNγ than in control mice treated with PBS. Moreover, treatment with ISAg activated CD4+ and CD8+ T cells as well as NK and NKT cells, resulting in the secretion of Th1-type cytokines in a toll-like receptor 4 (TLR4)-dependent manner, implying that TLR4 is critical for an optimal Th1 response. Interestingly, ISAg treatment increased the number of Foxp3+ Treg cells, but not of Th2 cells, compared to control mice treated with PBS, indicating that ISAg possesses an immunomodulatory capacity that can control adaptive immune responses. Taken together, our results indicate that ISAg possesses a Th1-enhancing activity that could be used to treat Th2-mediated allergic immune diseases such as atopic dermatitis. 相似文献