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91.
shRNA knockdown of Bmi-1 reveals a critical role for p21-Rb pathway in NSC self-renewal during development 总被引:7,自引:0,他引:7
Knockout studies have shown that the polycomb gene Bmi-1 is important for postnatal, but not embryonic, neural stem cell (NSC) self-renewal and have identified the cell-cycle inhibitors p16/p19 as molecular targets. Here, using lentiviral-delivered shRNAs in vitro and in vivo, we determined that Bmi-1 is also important for NSC self-renewal in the embryo. We found that neural progenitors depend increasingly on Bmi-1 for proliferation as development proceeds from embryonic through adult stages. Acute shRNA-mediated Bmi-1 reduction causes defects in embryonic and adult NSC proliferation and self-renewal that, unexpectedly, are mediated by a different cell-cycle inhibitor, p21. Gene array analyses revealed developmental differences in Bmi-1-controlled expression of genes in the p21-Rb cell cycle regulatory pathway. Our data therefore implicate p21 as an important Bmi-1 target in NSCs, potentially with stage-related differences. Understanding stage-related mechanisms underlying NSC self-renewal has important implications for development of stem cell-based therapies. 相似文献
92.
Kost L. A. Iunusova V. A. Ivanova V. O. Nikitin E. S. Lukyanov K. A. Bogdanov A. M. 《Russian Journal of Bioorganic Chemistry》2022,48(3):617-620
Russian Journal of Bioorganic Chemistry - In this study, we first used prestin, an electromotive protein of the mammalian auditory analyzer, as a voltage-sensitive core of a genetically encoded... 相似文献
93.
Simonenko E. Yu. Pryadun V. V. Ivanova A. A. Burmistrova E. V. Vasiliev A. N. Yakovenko S. A. 《Biophysics》2019,64(1):1-6
Biophysics - Abstract—The efficiency of cryoprotectants used to protect cells from damage is usually evaluated by the changes in vital cell parameters after a freezing–thawing cycle.... 相似文献
94.
Dudylina A. L. Ivanova M. V. Kalatanova A. V. Kalenikova E. I. Makarov V. G. Makarova M. N. Shumaev K. B. Ruuge E. K. 《Biophysics》2019,64(2):203-208
Biophysics - We have studied the effect of the water-soluble form of ubiquinol-10 (CoQ10-H2) on the processes of electron transport, oxidative phosphorylation, and the formation of reactive oxygen... 相似文献
95.
Lia Di Saymon Akther Edgaras Bezrucenkovas Larisa Ivanova Brian Sulkow Bing Wu Saad Mneimneh Maria Gomes-Solecki Wei-Gang Qiu 《The ISME journal》2022,16(2):447
Natural populations of pathogens and their hosts are engaged in an arms race in which the pathogens diversify to escape host immunity while the hosts evolve novel immunity. This co-evolutionary process poses a fundamental challenge to the development of broadly effective vaccines and diagnostics against a diversifying pathogen. Based on surveys of natural allele frequencies and experimental immunization of mice, we show high antigenic specificities of natural variants of the outer surface protein C (OspC), a dominant antigen of a Lyme Disease-causing bacterium (Borrelia burgdorferi). To overcome the challenge of OspC antigenic diversity to clinical development of preventive measures, we implemented a number of evolution-informed strategies to broaden OspC antigenic reactivity. In particular, the centroid algorithm—a genetic algorithm to generate sequences that minimize amino-acid differences with natural variants—generated synthetic OspC analogs with the greatest promise as diagnostic and vaccine candidates against diverse Lyme pathogen strains co-existing in the Northeast United States. Mechanistically, we propose a model of maximum antigen diversification (MAD) mediated by amino-acid variations distributed across the hypervariable regions on the OspC molecule. Under the MAD hypothesis, evolutionary centroids display broad cross-reactivity by occupying the central void in the antigenic space excavated by diversifying natural variants. In contrast to vaccine designs based on concatenated epitopes, the evolutionary algorithms generate analogs of natural antigens and are automated. The novel centroid algorithm and the evolutionary antigen designs based on consensus and ancestral sequences have broad implications for combating diversifying pathogens driven by pathogen–host co-evolution.Subject terms: Population genetics, Bacterial genetics 相似文献
96.
William B Andreopoulos Alexander M Geller Miriam Lucke Jan Balewski Alicia Clum Natalia N Ivanova Asaf Levy 《Nucleic acids research》2022,50(3):e17
Plasmids are mobile genetic elements that play a key role in microbial ecology and evolution by mediating horizontal transfer of important genes, such as antimicrobial resistance genes. Many microbial genomes have been sequenced by short read sequencers and have resulted in a mix of contigs that derive from plasmids or chromosomes. New tools that accurately identify plasmids are needed to elucidate new plasmid-borne genes of high biological importance. We have developed Deeplasmid, a deep learning tool for distinguishing plasmids from bacterial chromosomes based on the DNA sequence and its encoded biological data. It requires as input only assembled sequences generated by any sequencing platform and assembly algorithm and its runtime scales linearly with the number of assembled sequences. Deeplasmid achieves an AUC–ROC of over 89%, and it was more accurate than five other plasmid classification methods. Finally, as a proof of concept, we used Deeplasmid to predict new plasmids in the fish pathogen Yersinia ruckeri ATCC 29473 that has no annotated plasmids. Deeplasmid predicted with high reliability that a long assembled contig is part of a plasmid. Using long read sequencing we indeed validated the existence of a 102 kb long plasmid, demonstrating Deeplasmid''s ability to detect novel plasmids. 相似文献
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100.
Ivanova EV Koroleva IV Kuznetsov SB Aksenovich TI Svishcheva GR Mal'chenko SN Bendixen C Zhdanova NS 《Genetika》2001,37(2):230-237
In recent years, maps of mammalian genomes have been acquiring increasingly higher resolution. Integration of maps of different types has become possible. As a tool in integrating maps of mammalian genomes of different types, high-resolution mapping with radiation-induced hybrids (RH) is used. Here, we present an RH6000 map of the short arm of porcine chromosome 2. The map contains 15 microsatellites and five genes (for parathyroid hormone, lactate dehydrogenase A, myogenic factor, follicle-stimulating hormone beta, and calpain I). The RH panel was obtained on the basis of a hybrid cell line bearing the single porcine chromosome 2 against the background of mink chromosomes. The mean frequency of preserving markers examined in the panel was 18.3%. Integration of four genes in the panel and a comparison of gene order in homologous regions of human and porcine chromosomes are presented. 相似文献