全文获取类型
收费全文 | 666篇 |
免费 | 34篇 |
出版年
2022年 | 2篇 |
2021年 | 6篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 16篇 |
2016年 | 11篇 |
2015年 | 16篇 |
2014年 | 26篇 |
2013年 | 45篇 |
2012年 | 38篇 |
2011年 | 53篇 |
2010年 | 16篇 |
2009年 | 28篇 |
2008年 | 46篇 |
2007年 | 50篇 |
2006年 | 36篇 |
2005年 | 45篇 |
2004年 | 30篇 |
2003年 | 36篇 |
2002年 | 26篇 |
2001年 | 7篇 |
2000年 | 13篇 |
1999年 | 16篇 |
1998年 | 14篇 |
1997年 | 4篇 |
1996年 | 7篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 5篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1984年 | 3篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1979年 | 6篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1975年 | 2篇 |
1974年 | 6篇 |
1973年 | 3篇 |
1971年 | 2篇 |
1969年 | 2篇 |
1968年 | 1篇 |
排序方式: 共有700条查询结果,搜索用时 15 毫秒
101.
Bethke G Pecher P Eschen-Lippold L Tsuda K Katagiri F Glazebrook J Scheel D Lee J 《Molecular plant-microbe interactions : MPMI》2012,25(4):471-480
Mitogen-activated protein kinases (MAPK) mediate cellular signal transduction during stress responses, as well as diverse growth and developmental processes in eukaryotes. Pathogen infection or treatments with conserved pathogen-associated molecular patterns (PAMPs) such as the bacterial flagellin-derived flg22 peptide are known to activate three Arabidopsis thaliana MAPK: MPK3, MPK4, and MPK6. Several stresses, including flg22 treatment, are known to increase MPK11 expression but activation of MPK11 has not been shown. Here, we show that MPK11 activity can, indeed, be increased through flg22 elicitation. A small-scale microarray for profiling defense-related genes revealed that cinnamyl alcohol dehyrogenase 5 requires MPK11 for full flg22-induced expression. An mpk11 mutant showed increased flg22-mediated growth inhibition but no altered susceptibility to Pseudomonas syringae, Botrytis cinerea, or Alternaria brassicicola. In mpk3, mpk6, or mpk4 backgrounds, MPK11 is required for embryo or seed development or general viability. Although this developmental deficiency in double mutants and the lack of or only subtle mpk11 phenotypes suggest functional MAPK redundancies, comparison with the paralogous MPK4 reveals distinct functions. Taken together, future investigations of MAPK roles in stress signaling should include MPK11 as a fourth PAMP-activated MAPK. 相似文献
102.
Wnt proteins are secreted glycoproteins that bind to the N-terminal extra-cellular cysteine-rich domain of the Frizzled (Fzd) receptor family. The Fzd receptors can respond to Wnt proteins in the presence of Wnt co-receptors to activate the canonical and non-canonical Wnt pathways. Recent studies indicated that, among the Fzd family, Fzd7 is the Wnt receptor most commonly upregulated in a variety of cancers including colorectal cancer, hepatocellular carcinoma and triple negative breast cancer. Fzd7 plays an important role in stem cell biology and cancer development and progression. In addition, it has been demonstrated that siRNA knockdown of Fzd7, the anti-Fzd7 antibody or the extracellular peptide of Fzd7 (soluble Fzd7 peptide) displayed anti-cancer activity in vitro and in vivo mainly due to the inhibition of the canonical Wnt signaling pathway. Furthermore, pharmacological inhibition of Fzd7 by small interfering peptides or a small molecule inhibitor suppressed β-catenin-dependent tumor cell growth. Therefore, targeted inhibition of Fzd7 represents a rational and promising new approach for cancer therapy. 相似文献
103.
104.
Estrogen-like activity and dual roles in cell signaling of an Agaricus blazei Murrill mycelia-dikaryon extract 总被引:1,自引:0,他引:1
105.
Ito S Fujiyama-Nakamura S Kimura S Lim J Kamoshida Y Shiozaki-Sato Y Sawatsubashi S Suzuki E Tanabe M Ueda T Murata T Kato H Ohtake F Fujiki R Miki T Kouzmenko A Takeyama K Kato S 《Molecular cell》2012,45(4):494-504
Cell cycle-dependent expression of canonical histone proteins enables newly synthesized DNA to be integrated into chromatin in replicating cells. However, the molecular basis of cell cycle-dependency in the switching of histone gene regulation remains to be uncovered. Here, we report the identification and biochemical characterization of a molecular switcher, HERS (histone gene-specific epigenetic repressor in late S phase), for nucleosomal core histone gene inactivation in Drosophila. HERS protein is phosphorylated by a cyclin-dependent kinase (Cdk) at the end of S-phase. Phosphorylated HERS binds to histone gene regulatory regions and anchors HP1 and Su(var)3-9 to induce chromatin inactivation through histone H3 lysine 9 methylation. These findings illustrate a salient molecular switch linking epigenetic gene silencing to cell cycle-dependent histone production. 相似文献
106.
Abhinav Kumar Sabine M?cklinghoff Fumiaki Yumoto Lukasz Jaroszewski Carol L. Farr Anna Grzechnik Phuong Nguyen Christian X. Weichenberger Hsiu-Ju Chiu Heath E. Klock Marc-André Elsliger Ashley M. Deacon Adam Godzik Scott A. Lesley Bruce R. Conklin Robert J. Fletterick Ian A. Wilson 《PloS one》2012,7(9)
107.
Tange Y Kurabayashi A Goto B Hoe KL Kim DU Park HO Hayles J Chikashige Y Tsutumi C Hiraoka Y Yamao F Nurse P Niwa O 《PLoS genetics》2012,8(6):e1002776
To identify the genes required to sustain aneuploid viability, we screened a deletion library of non-essential genes in the fission yeast Schizosaccharomyces pombe, in which most types of aneuploidy are eventually lethal to the cell. Aneuploids remain viable for a period of time and can form colonies by reducing the extent of the aneuploidy. We hypothesized that a reduction in colony formation efficiency could be used to screen for gene deletions that compromise aneuploid viability. Deletion mutants were used to measure the effects on the viability of spores derived from triploid meiosis and from a chromosome instability mutant. We found that the CCR4-NOT complex, an evolutionarily conserved general regulator of mRNA turnover, and other related factors, including poly(A)-specific nuclease for mRNA decay, are involved in aneuploid viability. Defective mutations in CCR4-NOT complex components in the distantly related yeast Saccharomyces cerevisiae also affected the viability of spores produced from triploid cells, suggesting that this complex has a conserved role in aneuploids. In addition, our findings suggest that the genes required for homologous recombination repair are important for aneuploid viability. 相似文献
108.
Katakai T Suto H Sugai M Gonda H Togawa A Suematsu S Ebisuno Y Katagiri K Kinashi T Shimizu A 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(9):6189-6200
Mesenchymal stromal cells are crucial components of secondary lymphoid organs (SLOs). Organogenesis of SLOs involves specialized stromal cells, designated lymphoid tissue organizer (LTo) in the embryonic anlagen; in the adult, several distinct stromal lineages construct elaborate tissue architecture and regulate lymphocyte compartmentalization. The relationship between the LTo and adult stromal cells, however, remains unclear, as does the precise number of stromal cell types that constitute mature SLOs are unclear. From mouse lymph nodes, we established a VCAM-1(+)ICAM-1(+)MAdCAM-1(+) reticular cell line that can produce CXCL13 upon LTbetaR stimulation and support primary B cell adhesion and migration in vitro. A similar stromal population sharing many characteristics with the LTo, designated marginal reticular cells (MRCs), was found in the outer follicular region immediately underneath the subcapsular sinus of lymph nodes. Moreover, MRCs were commonly observed at particular sites in various SLOs even in Rag2(-/-) mice, but were not found in ectopic lymphoid tissues, suggesting that MRCs are a developmentally determined element. These findings lead to a comprehensive view of the stromal composition and architecture of SLOs. 相似文献
109.
110.
Natsume T Tsutsui Y Sutani T Dunleavy EM Pidoux AL Iwasaki H Shirahige K Allshire RC Yamao F 《PloS one》2008,3(5):e2221
Specialized chromatin exists at centromeres and must be precisely transmitted during DNA replication. The mechanisms involved in the propagation of these structures remain elusive. Fission yeast centromeres are composed of two chromatin domains: the central CENP-A(Cnp1) kinetochore domain and flanking heterochromatin domains. Here we show that fission yeast Mcl1, a DNA polymerase alpha (Pol alpha) accessory protein, is critical for maintenance of centromeric chromatin. In a screen for mutants that alleviate both central domain and outer repeat silencing, we isolated several cos mutants, of which cos1 is allelic to mcl1. The mcl1-101 mutation causes reduced CENP-A(Cnp1) in the central domain and an aberrant increase in histone acetylation in both domains. These phenotypes are also observed in a mutant of swi7(+), which encodes a catalytic subunit of Pol alpha. Mcl1 forms S-phase-specific nuclear foci, which colocalize with those of PCNA and Pol alpha. These results suggest that Mcl1 and Pol alpha are required for propagation of centromere chromatin structures during DNA replication. 相似文献