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73.
Site-specifically modified 2′-methylseleno RNA represents a valuable derivative for phasing of X-ray crystallographic data. Several successful applications in three-dimensional structure determination of nucleic acids, such as the Diels–Alder ribozyme, have relied on this modification. Here, we introduce synthetic routes to 2′-methylseleno phosphoramidite building blocks of all four standard nucleosides, adenosine, cytidine, guanosine and uridine, that are tailored for 2′-O-bis(acetoxyethoxy)methyl (ACE) RNA solid-phase synthesis. We additionally report on their incorporation into oligoribonucleotides including deprotection and purification. The methodological expansion of 2′-methylseleno labeling via ACE RNA chemistry is a major step to make Se-RNA generally accessible and to receive broad dissemination of the Se-approach for crystallographic studies on RNA. Thus far, preparation of 2′-methylseleno-modified oligoribonucleotides has been restricted to the 2′-O-[(triisopropylsilyl)oxy]methyl (TOM) and 2′-O-tert-butyldimethylsilyl (TBDMS) RNA synthesis methods. 相似文献
74.
Couillard-Despres S Finkl R Winner B Ploetz S Wiedermann D Aigner R Bogdahn U Winkler J Hoehn M Aigner L 《Molecular imaging》2008,7(1):28-34
Adult neurogenesis is a highly dynamic process modulated by several pathologic and environmental factors, as well as by various compounds. So far, available techniques to study neurogenesis are lengthy and personnel and cost intensive. We developed a new tool based on the doublecortin promoter driving the expression of the luciferase reporter gene (DCX-promo-luciferase) in transgenic mice to perform in vivo imaging of neurogenesis. Indeed, the DCX-promo-luciferase mice allowed optical in vivo imaging of the onset of and increase in neurogenesis in developing fetal brains, as well as imaging of neurogenesis in the intact adult mouse central nervous system. Moreover, the capacity to specifically detect a small number of migrating neuronal precursors in vivo after transplantation is for the first time feasible using this DCX-promo-luciferase transgenic tool. The present imaging approach offers several crucial advantages over methods currently available, such as bromodeoxyuridine incorporation or labeling using iron oxide nanoparticles. Hence, it allows longitudinal study of neurogenesis in intact animals without the requirement of cellular prelabeling. Moreover, it guarantees that detection is specific for neuronal precursors and restricted to viable cells. Hence, our DCX-promo-luciferase transgenic model constitutes an effective tool that answers the pressing need for rapid investigation of the impact on neurogenesis of a large number of candidate compounds waiting to be tested. 相似文献
75.
Ciaran Powers Achim Aigner Gerald E Stoica Kevin McDonnell Anton Wellstein 《The Journal of biological chemistry》2002,277(16):14153-14158
Glioblastoma multiforme is the most common highly aggressive human brain cancer, and receptor tyrosine kinases have been implicated in the progression of this malignancy. We have recently identified anaplastic lymphoma kinase (ALK) as a tyrosine kinase receptor for pleiotrophin, a secreted growth factor that is highly expressed during embryonic brain development and in tumors of the central nervous system. Here we report on the contribution of pleiotrophin-ALK signaling to glioblastoma growth. We found ALK overexpressed in human glioblastoma relative to normal brain and detected ALK mRNA in glioblastoma cell lines. We reduced the endogenous ALK in glioblastoma cells by ribozyme targeting and demonstrated that this prevents pleiotrophin-stimulated phosphorylation of the anti-apoptotic protein Akt. Furthermore, this depletion of ALK reduced tumor growth of xenografts in athymic nude mice and prolonged survival of the animals because of increased apoptosis in the tumors. These findings directly implicate ALK signaling as a rate-limiting factor in the growth of glioblastoma multiforme and suggest potential utility of therapeutic targeting of ALK. 相似文献
76.
Microsporidia, amitochondrial protists, possess a 70-kDa heat shock protein gene of mitochondrial evolutionary origin 总被引:13,自引:3,他引:10
Peyretaillade E; Broussolle V; Peyret P; Metenier G; Gouy M; Vivares CP 《Molecular biology and evolution》1998,15(6):683-689
An intronless gene encoding a protein of 592 amino acid residues with
similarity to 70-kDa heat shock proteins (HSP70s) has been cloned and
sequenced from the amitochondrial protist Encephalitozoon cuniculi (phylum
Microsporidia). Southern blot analyses show the presence of a single gene
copy located on chromosome XI. The encoded protein exhibits an N-terminal
hydrophobic leader sequence and two motifs shared by proteobacterial and
mitochondrially expressed HSP70 homologs. Phylogenetic analysis using
maximum likelihood and evolutionary distances place the E. cuniculi
sequence in the cluster of mitochondrially expressed HSP70s, with a higher
evolutionary rate than those of homologous sequences. Similar results were
obtained after cloning a fragment of the homologous gene in the closely
related species E. hellem. The presence of a nuclear targeting signal-like
sequence supports a role of the Encephalitozoon HSP70 as a molecular
chaperone of nuclear proteins. No evidence for cytosolic or endoplasmic
reticulum forms of HSP70 was obtained through PCR amplification. These data
suggest that Encephalitozoon species have evolved from an ancestor bearing
mitochondria, which is in disagreement with the postulated presymbiotic
origin of Microsporidia. The specific role and intracellular localization
of the mitochondrial HSP70-like protein remain to be elucidated.
相似文献
77.
Rabitsch KP Tóth A Gálová M Schleiffer A Schaffner G Aigner E Rupp C Penkner AM Moreno-Borchart AC Primig M Esposito RE Klein F Knop M Nasmyth K 《Current biology : CB》2001,11(13):1001-1009
BACKGROUND: Meiosis is the process by which gametes are generated with half the ploidy of somatic cells. This reduction is achieved by three major differences in chromosome behavior during meiosis as compared to mitosis: the production of chiasmata by recombination, the protection of centromere-proximal sister chromatid cohesion, and the monoorientation of sister kinetochores during meiosis I. Mistakes in any of these processes lead to chromosome missegregation. RESULTS: To identify genes involved in meiotic chromosome behavior in Saccharomyces cerevisiae, we deleted 301 open reading frames (ORFs) which are preferentially expressed in meiotic cells according to microarray gene expression data. To facilitate the detection of chromosome missegregation mutants, chromosome V of the parental strain was marked by GFP. Thirty-three ORFs were required for the formation of wild-type asci, eight of which were needed for proper chromosome segregation. One of these (MAM1) is essential for the monoorientation of sister kinetochores during meiosis I. Two genes (MND1 and MND2) are implicated in the recombination process and another two (SMA1 and SMA2) in prospore membrane formation. CONCLUSIONS: Reverse genetics using gene expression data is an effective method for identifying new genes involved in specific cellular processes. 相似文献
78.
Hubert Pausch Bernhard Aigner Reiner Emmerling Christian Edel Kay-Uwe G?tz Ruedi Fries 《遗传、选种与进化》2013,45(1):3
Background
Currently, genome-wide evaluation of cattle populations is based on SNP-genotyping using ~ 54 000 SNP. Increasing the number of markers might improve genomic predictions and power of genome-wide association studies. Imputation of genotypes makes it possible to extrapolate genotypes from lower to higher density arrays based on a representative reference sample for which genotypes are obtained at higher density.Methods
Genotypes using 639 214 SNP were available for 797 bulls of the Fleckvieh cattle breed. The data set was divided into a reference and a validation population. Genotypes for all SNP except those included in the BovineSNP50 Bead chip were masked and subsequently imputed for animals of the validation population. Imputation of genotypes was performed with Beagle, findhap.f90, MaCH and Minimac. The accuracy of the imputed genotypes was assessed for four different scenarios including 50, 100, 200 and 400 animals as reference population. The reference animals were selected to account for 78.03%, 89.21%, 97.47% and > 99% of the gene pool of the genotyped population, respectively.Results
Imputation accuracy increased as the number of animals and relatives in the reference population increased. Population-based algorithms provided highly reliable imputation of genotypes, even for scenarios with 50 and 100 reference animals only. Using MaCH and Minimac, the correlation between true and imputed genotypes was > 0.975 with 100 reference animals only. Pre-phasing the genotypes of both the reference and validation populations not only provided highly accurate imputed genotypes but was also computationally efficient. Genome-wide analysis of imputation accuracy led to the identification of many misplaced SNP.Conclusions
Genotyping key animals at high density and subsequent population-based genotype imputation yield high imputation accuracy. Pre-phasing the genotypes of the reference and validation populations is computationally efficient and results in high imputation accuracy, even when the reference population is small. 相似文献79.
Langguth B Braun S Aigner JM Landgrebe M Weinerth J Hajak G Eichhammer P 《Neuro endocrinology letters》2005,26(4):314-316
Repetitive transcranial magnetic stimulation (rTMS) has been suggested as antidepressive treatment strategy. The mechanism of action by which the antidepressive effect is brought about remains unclear at present. Here, we report findings in a patient suffering from recurrent major depression and rheumatoid arthritis. Improvement of depressive symptoms during 20 Hz rTMS of the left dorsolateral prefrontal cortex was repeatedly associated with a systemic inflammatory reaction, suggesting that rTMS induced an immunomodulatory effect. 相似文献
80.