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51.
Stephen Neidle 《Biopolymers》1997,44(1):105-121
This review surveys the crystal structures between minor groove drugs and oligonucleotides, of which over thirty have now been determined. The various factors that are involved in the observed A/T sequence selectivity of these drugs are examined in structural terms. The roles of, in particular, hydrogen-bond recognition and sequence-dependent groove width, are assessed, and as a consequence the minor groove drugs have been classified into two categories, dependent on the relative roles played by these two factors in sequence recognition. Implications for the recognition of non-A/T sequences are discussed. © 1997 John Wiley & Sons, Inc. Biopoly 44: 105–121, 1997 相似文献
52.
Peter Nilsson Bjrn Persson Anita Larsson Mathias Uhln Per-ke Nygren 《Journal of molecular recognition : JMR》1997,10(1):7-17
Two different strategies for scanning and screening of mutations in polymerase chain reaction (PCR) products by hybridization analysis are described, employing real-time biospecific interaction analysis (BIA) for detection. Real-time BIA was used to detect differences in hybridization responses between PCR products and different 17-mer oligonucleotide probes. For the analysis using a biosensor instrument, two different experimental formats were investigated based on immobilization of either biotinylated PCR products or oligonucleotide probes onto a sensor chip. Applied on the human tumour suppressor p53 gene, differences in hybridization levels for full-match and mismatch situations employing both formats allowed the detection of point mutations in exon 6 PCR products, derived from a breast tumour biopsy sample. In addition, a mutant sample sequence could be detected in a 50/50 background of wild type exon 6 sequence. The suitability of the different formats for obtaining a regenerable system and a high throughput of samples is discussed. © 1997 John Wiley & Sons, Ltd. 相似文献
53.
A. S. Levina E. A. Mikhaleva M. N. Repkova V. F. Zarytova 《Russian Journal of Bioorganic Chemistry》2008,34(1):80-86
A simple and efficient method of synthesis of polyamine-oligonucleotide conjugates (PA-oligos) in high yields (up to 95%) was suggested. The terminal phosphate group of deprotected oligonucleotides was selectively activated with the redox pair triphenylphosphine-dipyridyl disulfide in the presence of a nucleophilic catalyst, and the activated oligonucleotide derivative was subjected to the reaction with a polyamine. 相似文献
54.
55.
Eric Wickstrom Mathew L. Thakur Edward R. Sauter 《International journal of peptide research and therapeutics》2003,10(3-4):191-214
Summary Genomic sequencing makes it possible to identify all the genes of an organism, now includingHomo sapiens. Yet measurement of the expression of each gene of interest still presents a daunting prospect. Northern blots, RNase protection
assays, as well as microarrays and related technologies permit measurement of gene expression in total RNA extracted from
cultured cells or tissue samples. It would be most valuable, however, to quantitate gene expression noninvasively in living
cells and tissues. Unfortunately, no reliable method has been available to measure levels of specific mRNAsin vivo. Peptide nucleic acids (PNAs) display superior ruggedness and hybridization properties as a diagnostic tool for gene expression,
and could be used for this purpose. On the down side, they are negligibly internalized by normal or malignant cells in the
absence of conjugated ligands. Nevertheless, we have observed that Tc-99m-peptides can delineate tumors, and PNA-peptides
designed to bind to IGF-1 receptors on malignant cells are taken up specifically and concentrated in nuclei. We have postulated
that antisense Tc-99m-PNA-peptides will be taken up by human cancer cells, will hybridize to complementary mRNA targets, and
will permit scintigraphic imaging of oncogene mRNAs in human cancer xenografts in a mouse model. The oncogenes cyclin D1,ERBB2, c-MYC, K-RAS, and tumor suppressor p53 are being probed initially. These experiments provide a proof-of-principle for noninvasive detection
of oncogene expression in living cells and tissues. This scintigraphic imaging technique should be applicable to any particular
gene of interest in a cell or tissue type with characteristic receptors. 相似文献
56.
A. S. Pavlova P. E. Vorobyev V. F. Zarytova 《Russian Journal of Bioorganic Chemistry》2009,35(2):197-206
Monofunctional conjugates of 15-mer triplex-forming oligonucleotide (TFO) with covalently attached bleomycin A5 residue at the 5′-end (Blm-p15) were synthesized. Bifunctional conjugates of TFO containing, in addition to Blm, the residues of intercalator 6-chloro-2-methoxy-9-aminoacridine (Acr) or N-(2-hydroxyethyl)phenazinium (Phn) were obtained for the first time. The Acr and Phn residues were attached to the 3′-phosphate group of TFO through L1 and L2 linkers, respectively, resulting in the compounds Blmp15pL1-Acr and Blm-p15pL2-Phn. The values of dissociation constants of the corresponding triplexes were evaluated using the gel retardation method. The Acr residue in Blm-p15pL1-Acr was shown to enhance the stability of the formed triplex by one order of magnitude. It was demonstrated that all synthesized conjugates are capable of specifically and nonspecifically damaging a target DNA, forming direct breaks and alkaline-labile sites. The extent of the specific cleavage of the target DNA was 15% in the case of a fivefold excess of the conjugates over the DNA duplex. The site-specific triplex-mediated cleavage of a target DNA was shown for the first time to occur predominantly (>90%) with the formation of the direct breaks of both DNA strands. The results show the availability of bleomycin-containing oligonucleotides as antigene compounds. 相似文献
57.
The chemical behavior of sulfur-containing oligonucleotides and their reactivity in self-assembled nucleic acids (NA) and specific NA–protein complexes is considered. Reviewed are postsynthetic approaches that allow introducing sulfur-containing linkages at preselected positions of the sugar-phosphate backbone of DNA and between neighboring nucleobases, to incorporate disulfide bridges between complementary strands of double- and triple-stranded DNAs, in large catalytic RNA, etc. Special reference is given to the site-specific chemical modifications as a tool for elucidating the structure, folding, and function of biomolecules. Structure-directed chemical reactions are shown to be helpful in detecting point mutations in DNA, targeting the modifications on specific positions of NA, probing the molecular recognition in protein–DNA interfaces, studying the conformational dynamics of nucleic acids, and discriminating between different folding models. 相似文献
58.
L. M. Skobeltsyna D. V. Pyshnyi I. G. Shishkina D. R. Tabatadze G. M. Dymshits V. F. Zarytova E. M. Ivanova 《Molecular Biology》2000,34(3):321-327
A new approach for detection of point mutations has been developed. The nonradioactive test system proposed is based on enzymatic
ligation of a tandem of three short oligonucleotides B∼pN8+pN4+pN′8 Bio in the presence of a complementary DNA template. The 5′-terminal octanucleotide B∼pN8 is immobilized on polymer methacrylate beads (B) and the 3′-terminal octanucleotide pN′8 Bio contains a biotin residue at the 3′-phosphate. Ligation of the tandem produces a 20-mer biotinylated oligonucleotide
on a polymer bead, which is then visualized via subsequent treatments with streptavidin-alkaline phosphatase conjugate and
chromogenic substrates. Intense staining of the polymer beads is observed when the amount of DNA template (20-mer oligonucleotide)
is as low as ∼10−14 mol. It is shown that practically no polymer staining is observed when the complex formed by the tandem and the 20-mer DNA
template contains a mismatch either in the tetranucleotide duplex or in the duplex of octanucleotide immobilized on the beads.
This suggests a possibility of using the presented approach in test systems for detection of point mutations in PCR-amplified
DNA fragments. 相似文献
59.
RNA/DNA嵌合分子介导的高效基因修复 总被引:2,自引:1,他引:1
本文介绍了RNA/DNA嵌合分子介导的高效基因修复技术。这一技术是1996年开始发展起来的全新技术,它通过人工合成的双链开环RNA/DNA嵌合分子转染细胞而使特定基因靶位点产生单碱基改变,从而修复突变基因。这一技术高效(目前最高可达50%以上)、特异性强、安全、无随机插入致变的危险、无免疫反应、无明显毒性,能够用于定点突变、基因敲除、动植物功能基因组学、药物遗传学等很多方面的研究,在不久的将来能够应用于人类基因治疗,具有很高的应用价值和医学前景。
Abstract:We introduce a new technique?targeted gene correction directed by chimeric RNA/DNA oligonucleotides which began at 1996.It uses synthetic double?stranded non?circular RNA/DNA chimeric oligonucleotides to transfect cells and make a single?based change at the targeted site of the target gene.It is highly efficient (the highest efficiency is more than 50%),highly special,safe,without danger of mutation caused by random insertion,without immune response,and without obvious toxicity.It can be used to make point mutation,or gene knock?out plants and animals,and is very likely to be used in human gene therapy in the near future.It is also valuable in the study of functional genomics,pharmacogenetics,and medicine. 相似文献
60.