全文获取类型
收费全文 | 393篇 |
免费 | 40篇 |
专业分类
433篇 |
出版年
2022年 | 3篇 |
2021年 | 4篇 |
2019年 | 5篇 |
2018年 | 4篇 |
2016年 | 8篇 |
2015年 | 8篇 |
2014年 | 9篇 |
2013年 | 17篇 |
2012年 | 18篇 |
2011年 | 16篇 |
2010年 | 13篇 |
2009年 | 8篇 |
2008年 | 11篇 |
2007年 | 12篇 |
2006年 | 6篇 |
2005年 | 13篇 |
2004年 | 10篇 |
2003年 | 13篇 |
2002年 | 21篇 |
2001年 | 12篇 |
2000年 | 12篇 |
1999年 | 9篇 |
1997年 | 9篇 |
1996年 | 8篇 |
1995年 | 5篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 11篇 |
1991年 | 8篇 |
1990年 | 10篇 |
1989年 | 10篇 |
1988年 | 7篇 |
1987年 | 11篇 |
1986年 | 9篇 |
1985年 | 8篇 |
1984年 | 6篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 10篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1969年 | 3篇 |
1968年 | 2篇 |
1967年 | 5篇 |
1965年 | 4篇 |
1964年 | 5篇 |
排序方式: 共有433条查询结果,搜索用时 10 毫秒
371.
Fernández-López M Muñoz-Adelantado E Gillis M Willems A Toro N 《Molecular biology and evolution》2005,22(6):1518-1528
Group II introns are both self-splicing RNAs and mobile retroelements found in bacterial and archaeal genomes and in organelles of eukaryotes. They are thought to be the ancestors of eukaryote spliceosomal introns and non-long terminal repeat retrotransposons. We show here that RmInt1, a bacterial group II intron first described in the nitrogen-fixing symbiont of alfalfa (Medicago sativa) Sinorhizobium meliloti, is also present in other Sinorhizobium and Rhizobium species. The intron-homing sites in these species are IS elements of the ISRm2011-2 group as in S. meliloti, but ectopic insertion is also observed. We present evidence that these related bacteria have acquired RmInt1 by vertical inheritance from a common ancestor and by independent horizontal transfer events. We also show that RmInt1 is mobile in related taxa of bacteria that interact with plants and tends to evolve toward an inactive form by fragmentation, with loss of the 3' terminus including the intron-encoded protein. Our results provide an overview of the evolution and dispersion of a bacterial group II intron. 相似文献
372.
A novel role for the CBF3 kinetochore-scaffold complex in regulating septin dynamics and cytokinesis
In budding yeast, the kinetochore scaffold complex centromere binding factor 3 (CBF3) is required to form kinetochores on centromere DNA and to allow proper chromosome segregation. We have previously shown that SKP1 and SGT1 balance the assembly and turnover of CBF3 complexes, a cycle that we suggest is independent of its role in chromosome segregation (Rodrigo-Brenni, M.C., S. Thomas, D.C. Bouck, and K.B. Kaplan. 2004. Mol. Biol. Cell. 15:3366-3378). We provide evidence that this cycle contributes to a second, kinetochore-independent function of CBF3. In this study, we show that inhibiting the assembly of CBF3 causes disorganized septins and defects in cell polarity that give rise to cytokinesis failures. Specifically, we show that septin ring separation and disassembly is delayed in anaphase, suggesting that CBF3 regulates septin dynamics. Only mutations that affect the CBF3 cycle, and not mutants in outer kinetochore subunits, cause defects in septins. These results demonstrate a novel role for CBF3 in regulating cytokinesis, a role that is reminiscent of passenger proteins. Consistent with this possibility, we find that CBF3 interacts with Bir1p, the homologue of the passenger protein Survivin. Mutants in Bir1p similarly affect septin organization, leading us to propose that CBF3 and Bir1p act as passenger proteins to coordinate chromosome segregation with cytokinesis. 相似文献
373.
Azizi E Gillis GB Brainerd EL 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2002,133(4):967-978
In contrast to the complex, three-dimensional shape of myomeres in teleost fishes, the lateral hypaxial muscles of salamanders are nearly planar and their myosepta run in a roughly straight line from mid-lateral to mid-ventral. We used this relatively simple system as the basis for a mathematical model of segmented musculature. Model results highlight the importance of the mechanics of myosepta in determining the shortening characteristics of a muscle segment. We used sonomicrometry to measure the longitudinal deformation of myomeres and the dorsoventral deformation of myosepta in a swimming salamander (Siren lacertina). Sonomicrometry results show that the myosepta allow some dorsoventral lengthening, indicating an amplification of myomere shortening that is greater than that produced by muscle fiber angle alone (10% muscle fiber shortening produces 28.7% myomere shortening). Polarized light and DIC microscopy of isolated hypaxial myosepta revealed that the collagen fiber orientation in hypaxial myomeres is primarily mediolateral. The mediolateral collagen fiber orientation, combined with our finding that the hypaxial myosepta lengthen dorsoventrally during swimming, suggests that one possible function of hypaxial myosepta in S. lacertina is to increase the strain amplification of the muscle fibers by reducing the mediolateral bulging of the myomeres and redirecting the bulging toward the dorsoventral direction. 相似文献
374.
Gillis TE Tibbits GF 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2002,132(4):763-772
The sensitivity of the cardiac myocyte contractile element for Ca(2+) decreases with temperature. As myocyte contractility is regulated by changes in cytosolic [Ca(2+)], this desensitizing effect represents a challenge for temperate fish such as the rainbow trout, Oncorhynchus mykiss, living in environments where temperatures are low and variable. To allow cardiac function in a temperate environment it is thought that the comparatively high Ca(2+) sensitivity of trout cardiac myocytes compensates for the effects of low temperature on myocyte contractility. The high Ca(2+) sensitivity of the trout myocyte is due, at least in part, to changes in the amino acid sequence of the thin filament protein, cardiac troponin C (cTnC). cTnC is the Ca(2+)-activated switch that triggers myocyte contraction. The isoform of cTnC cloned from trout ventricle (ScTnC) is 92% identical to mammalian cTnC (McTnC) and is significantly more sensitive to Ca(2+). This result suggests that ScTnC has evolved in trout to allow cardiac function at low temperatures. cTnC also appears to play a role in maintaining cardiac function when temperatures change. Increasing myofibrillar pH according to alpha-stat regulation, as would occur when temperature decreases, increases Ca(2+) sensitivity. A similar increase in pH also sensitizes cTnC to Ca(2+). ScTnC therefore appears critical in maintaining cardiac function in trout at low temperatures as well as during changes in temperature. 相似文献
375.
Chen B Borinstein SC Gillis J Sykes VW Bogler O 《The Journal of biological chemistry》2000,275(25):19275-19281
Expression of the src homology 3 (SH3) domain-containing expressed in tumorigenic astrocytes (SETA) gene is associated with the tumorigenic state in astrocytes. SETA encodes a variety of adapter proteins containing either one or two SH3 domains, as suggested by the sequence heterogeneity of isolated cDNAs. Using both SH3 domains in a yeast two-hybrid screen of a glial progenitor cell cDNA library, we isolated the rat homolog of the ALG-2-interacting protein 1 or ALG-2-interacting protein X (AIP1/Alix). In vitro confrontation experiments showed that the SH3-N domain of SETA interacted with the proline-rich C terminus of AIP1. In co-immunoprecipitation experiments, SETA and AIP1 interacted and could form a complex with apoptosis-linked gene 2 protein. Endogenous SETA and AIP1 proteins showed similar patterns of staining in primary rat astrocytes. Misexpression of a variety of SETA protein isoforms in these astrocytes revealed that they localized to the actin cytoskeleton. Furthermore, SETA proteins containing the SH3-N domain were able to sensitize astrocytes to apoptosis induced by UV irradiation. Expression of the isolated SH3-N domain had the greatest effect in these experiments, indicating that interference in the interaction between endogenous SETA and AIP1 sensitizes astrocytes to apoptosis in response to DNA damage. 相似文献
376.
Schloe K Gillis M Hoste B Pot B Vancanneyt M Mergaert J Swings J Biedermann J Süssmuth R 《Systematic and applied microbiology》2000,23(3):364-372
For the purpose of denitrification in small drinking water plants, a bacterial mixed population was isolated from a packed bed column bioreactor with poly-3-hydroxybutyrate-co-3-hydroxyvalerate (P(HB-co-HV)) as a substrate for the denitrification of ground water (10 degrees C). Isolates 2nIII from the mixed culture, with the ability to denitrify and metabolize P(HB-co-HV), were used as starter cultures for the elimination of nitrate in ground water. The strains were characterized by diverse techniques. Classical phenotypic studies lead to rRNA group III of the genus Pseudomonas. Results obtained by molecular techniques demonstrated that the 2nIII strains are members of the Comamonadaceae and shows similarities to the genus Acidovorax. However, an integration of the 2nIII isolates within one of the known Acidovorax species is not possible for the moment. The 2nIII starter cultures clustered close to Av. temperans according to their whole cell proteins and fatty acids, whereas in DNA/DNA hybridization no significant DNA binding (< 25%) was found. In contrast a significant but low degree of DNA/DNA hybridization was found between the 2nIII strains and Av. facilis and Av. delafieldii. Our polyphasic results lead to the conclusion that the 2nIII strains may constitute a separate Acicdovorax species. 相似文献
377.
378.
379.
Mulder KW Wang X Escriu C Ito Y Schwarz RF Gillis J Sirokmány G Donati G Uribe-Lewis S Pavlidis P Murrell A Markowetz F Watt FM 《Nature cell biology》2012,14(7):753-763
It is becoming clear that interconnected functional gene networks, rather than individual genes, govern stem cell self-renewal and differentiation. To identify epigenetic factors that impact on human epidermal stem cells we performed siRNA-based genetic screens for 332 chromatin modifiers. We developed a Bayesian mixture model to predict putative functional interactions between epigenetic modifiers that regulate differentiation. We discovered a network of genetic interactions involving EZH2, UHRF1 (both known to regulate epidermal self-renewal), ING5 (a MORF complex component), BPTF and SMARCA5 (NURF complex components). Genome-wide localization and global mRNA expression analysis revealed that these factors impact two distinct but functionally related gene sets, including integrin extracellular matrix receptors that mediate anchorage of epidermal stem cells to their niche. Using a competitive epidermal reconstitution assay we confirmed that ING5, BPTF, SMARCA5, EZH2 and UHRF1 control differentiation under physiological conditions. Thus, regulation of distinct gene expression programs through the interplay between diverse epigenetic strategies protects epidermal stem cells from differentiation. 相似文献
380.
Eliana Marisa Ramos Jeanne C. Latourelle Ji-Hyun Lee Tammy Gillis Jayalakshmi S. Mysore Ferdinando Squitieri Alba Di Pardo Stefano Di Donato Michael R. Hayden Patrick J. Morrison Martha Nance Christopher A. Ross Russell L. Margolis Estrella Gomez-Tortosa Carmen Ayuso Oksana Suchowersky Ronald J. Trent Elizabeth McCusker Andrea Novelletto Marina Frontali Randi Jones Tetsuo Ashizawa Samuel Frank Marie-Helene Saint-Hilaire Steven M. Hersch Herminia D. Rosas Diane Lucente Madaline B. Harrison Andrea Zanko Karen Marder James F. Gusella Jong-Min Lee Isabel Alonso Jorge Sequeiros Richard H. Myers Marcy E. MacDonald 《Human genetics》2012,131(12):1833-1840
Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by motor, cognitive and behavioral disturbances, caused by the expansion of a CAG trinucleotide repeat in the HD gene. The CAG allele size is the major determinant of age at onset (AO) of motor symptoms, although the remaining variance in AO is highly heritable. The rs7665116 SNP in PPARGC1A, encoding the mitochondrial regulator PGC-1α, has been reported to be a significant modifier of AO in three European HD cohorts, perhaps due to affected cases from Italy. We attempted to replicate these findings in a large collection of (1,727) HD patient DNA samples of European origin. In the entire cohort, rs7665116 showed a significant effect in the dominant model (p value?=?0.008) and the additive model (p value?=?0.009). However, when examined by origin, cases of Southern European origin had an increased rs7665116 minor allele frequency (MAF), consistent with this being an ancestry-tagging SNP. The Southern European cases, despite similar mean CAG allele size, had a significantly older mean AO (p?<?0.001), suggesting population-dependent phenotype stratification. When the generalized estimating equations models were adjusted for ancestry, the effect of the rs7665116 genotype on AO decreased dramatically. Our results do not support rs7665116 as a modifier of AO of motor symptoms, as we found evidence for a dramatic effect of phenotypic (AO) and genotypic (MAF) stratification among European cohorts that was not considered in previously reported association studies. A significantly older AO in Southern Europe may reflect population differences in genetic or environmental factors that warrant further investigation. 相似文献