全文获取类型
收费全文 | 12717篇 |
免费 | 711篇 |
国内免费 | 1916篇 |
出版年
2024年 | 23篇 |
2023年 | 202篇 |
2022年 | 331篇 |
2021年 | 406篇 |
2020年 | 331篇 |
2019年 | 425篇 |
2018年 | 362篇 |
2017年 | 319篇 |
2016年 | 319篇 |
2015年 | 388篇 |
2014年 | 640篇 |
2013年 | 726篇 |
2012年 | 515篇 |
2011年 | 701篇 |
2010年 | 602篇 |
2009年 | 692篇 |
2008年 | 749篇 |
2007年 | 716篇 |
2006年 | 659篇 |
2005年 | 619篇 |
2004年 | 577篇 |
2003年 | 577篇 |
2002年 | 412篇 |
2001年 | 354篇 |
2000年 | 328篇 |
1999年 | 294篇 |
1998年 | 287篇 |
1997年 | 233篇 |
1996年 | 221篇 |
1995年 | 223篇 |
1994年 | 236篇 |
1993年 | 208篇 |
1992年 | 215篇 |
1991年 | 151篇 |
1990年 | 141篇 |
1989年 | 125篇 |
1988年 | 97篇 |
1987年 | 111篇 |
1986年 | 88篇 |
1985年 | 103篇 |
1984年 | 93篇 |
1983年 | 81篇 |
1982年 | 104篇 |
1981年 | 61篇 |
1980年 | 61篇 |
1979年 | 64篇 |
1978年 | 63篇 |
1977年 | 26篇 |
1976年 | 29篇 |
1974年 | 20篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
《Critical reviews in biochemistry and molecular biology》2013,48(4):337-397
Dedicated to Prof. Jan H. J. Hoeijmakers.Referee: Dr. Nawin C. Mishra, Professor of Genetics, University of South Carolina, Department of Biological Sciences, Columbia, SC 29208Despite stable genomes of all living organisms, they are subject to damage by chemical and physical agents in the environment (e.g., UV and ionizing radiations, chemical mutagens, fungal and bacterial toxins, etc.) and by free radicals or alkylating agents endogenously generated in metabolism. DNA is also damaged because of errors during its replication. The DNA lesions produced by these damaging agents could be altered base, missing base, mismatch base, deletion or insertion, linked pyrimidines, strand breaks, intra- and inter-strand cross-links. 相似文献
993.
《Critical reviews in biochemistry and molecular biology》2013,48(5):375-430
AbstractDespite the rapid mutational change that is typical of positive-strand RNA viruses, enzymes mediating the replication and expression of virus genomes contain arrays of conserved sequence motifs. Proteins with such motifs include RNA-dependent RNA polymerase, putative RNA helicase, chymotrypsin-like and papain-like proteases, and methyltransferases. The genes for these proteins form partially conserved modules in large subsets of viruses. A concept of the virus genome as a relatively evolutionarily stable “core” of housekeeping genes accompanied by a much more flexible “shell” consisting mostly of genes coding for virion components and various accessory proteins is discussed. Shuffling of the “shell” genes including genome reorganization and recombination between remote groups of viruses is considered to be one of the major factors of virus evolution.Multiple alignments for the conserved viral proteins were constructed and used to generate the respective phylogenetic trees. Based primarily on the tentative phylogeny for the RNA-dependent RNA polymerase, which is the only universally conserved protein of positive-strand RNA viruses, three large classes of viruses, each consisting of distinct smaller divisions, were delineated. A strong correlation was observed between this grouping and the tentative phylogenies for the other conserved proteins as well as the arrangement of genes encoding these proteins in the virus genome. A comparable correlation with the polymerase phylogeny was not found for genes encoding virion components or for genome expression strategies. It is surmised that several types of arrangement of the “shell” genes as well as basic mechanisms of expression could have evolved independently in different evolutionary lineages.The grouping revealed by phylogenetic analysis may provide the basis for revision of virus classification, and phylogenetic taxonomy of positive-strand RNA viruses is outlined. Some of the phylogenetically derived divisions of positive-strand RNA viruses also include double-stranded RNA viruses, indicating that in certain cases the type of genome nucleic acid may not be a reliable taxonomic criterion for viruses.Hypothetical evolutionary scenarios for positive-strand RNA viruses are proposed. It is hypothesized that all positive-strand RNA viruses and some related double-stranded RNA viruses could have evolved from a common ancestor virus that contained genes for RNA-dependent RNA polymerase, a chymotrypsin-related protease that also functioned as the capsid protein, and possibly an RNA helicase. 相似文献
994.
《Animal biotechnology》2013,24(1):77-86
This paper reports on the development of a small-insert (~700 bp) total-genomic library for sheep specifically designed for enrichment for microsatellite (ms) loci. Four enriched libraries were prepared by amplification of the primary library with CA15, CA11, TG15 and TG11 oligonucleotide primers. A total of 11,020 clones was recovered, screened for dinucleotide repeats and over 500 positive clones sequenced. Sequence analysis indicated low clone redundancy and yielded 105 new ovine ms loci. Seventy-two percent of the new loci were found to be polymorphic in the sires of the AgResearch International Mapping Flock (IMF). The 105 new microsatellite loci increase the number of microsatellites available for sheep by >7%. 相似文献
995.
G Gashi V Mahovlić E Bahtiri F Kurshumliu A Podrimaj-Bytyqi IR Elezaj 《Biotechnic & histochemistry》2013,88(7):496-504
Human papilloma virus (HPV) infection is the main etiological factor for cervical intraepithelial lesions (CIN). An important characteristic of this process is the loss of genome stability. Therefore, it is imperative to use biomarkers of DNA damage caused by genomic instability to identify high risk individuals. We investigated the frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) of 20 patients, diagnosed as histologically CIN 1 and 10 healthy controls. We also examined the frequency of other nuclear anomalies including nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in PBL of patients with CIN 1 and healthy controls, and evaluated the benefits of p16INK4a and Ki-67 (p16INK4a/Ki-67) immunohistochemical double staining for identifying cervical squamous cells that express HPV E6/E7 oncogenes. We analyzed the association between the frequency of MN in PBL and the amount of p16INK4a/Ki-67 co-expression in CIN 1 patients to establish genomic instability. Among CIN 1 subjects, 15% exhibited diffuse p16INK4a/Ki-67 co-expression and were considered high positive, 25% of the CIN 1 cases exhibited p16INK4a/Ki-67 co-expression restricted to the lower part of the epithelium and were considered low positive and the remaining 60% of cases were negative. The frequency of MN, NPBs and NBUDs differed significantly among groups. We found a statistically significant positive correlation between p16INK4a/Ki-67 co-expression and the frequency of MN, NPBs and NBUDs in PBL. Our findings demonstrate the efficacy of p16INK4a/Ki-67 double immunostaining for histological samples with CIN 1. MN frequency in PBL might be useful for detecting genomic instability in cases of HPV infection and CIN. 相似文献
996.
997.
Li‐Na Zhu Cai‐Yun Fu Shi‐Fu Zhang Wei Chen Yuan‐Ting Jin Fu‐Kun Zhao 《Journal of peptide science》2013,19(9):566-574
Anoplin is a recently discovered antimicrobial peptide (AMP) isolated from the venom sac of the spider wasp Anoplius samariensis, and it is one of the shortest α‐helical AMP found naturally to date consisting of only ten amino acids. Previous results showed that anoplin exhibits potent antimicrobial activity but little hemolytic activity. In this study, we synthesized anoplin, studied its cytotoxicity in Friend virus‐induced leukemia cells [murine erythroleukemia (MEL) cells], and proposed its possible mechanism. Our results showed that anoplin could inhibit the proliferation of MEL cells in a dose‐dependent and time‐dependent manner via disrupting the integrity of cell membrane, which indicated that anoplin exerts its cytotoxicity efficacy. In addition, the cell cycle distribution of MEL cells was arrested in the G0/G1 phase significantly. However, anoplin could not induce obvious apoptosis in MEL cells, as well as anoplin could not induce visible changes on morphology and quantity in the bone marrow cells isolated from normal mice. All of these results indicate that anoplin, as generally believed, is a selective AMP, a value characteristic in the design of safe therapeutic agents. The cytotoxicity of anoplin on MEL cells was mainly attributable to the plasma membrane perturbation and also to the intracellular events such as the arrest of cell cycle. Although this is an initial study that explored the activity of anoplin in vitro rather than in vivo, with the increasing resistance of conventional chemotherapy, there is no doubt that anoplin has desirable feature to be developed as a novel and selective anticancer agent. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
998.
999.
Ronald G. Duggleby 《Journal of enzyme inhibition and medicinal chemistry》2013,28(2):141-146
When an unstable enzyme is incubated with its substrate(s), catalysis may cease before chemical equilibrium is attained. The residual substrate concentrations depend on their initial concentrations, the initial enzymic activity, and the inactivation rate constants for each molecular species that comprise the catalytic cycle. The underlying theory has been elaborated previously for single-substrate reactions and here it is extended to bi-substrate reactions. The theory is illustrated by application to glucose 6-phosphate dehydrogenase, which is unstable when exposed to a low concentration of sodium dodecyl sulphate. It is shown that the ternary complex containing both substrates is resistant to inactivation while each of the remaining complexes undergoes first-order decay. Rate constants for the inactivation of each complex are calculated. 相似文献
1000.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):614-617
This article describes the photodynamic inactivation of mosquito iridescent virus (MIV) Aedes flavescens in the presence of water-soluble C60 fullerenes. It has been observed that the photodynamic inactivation of MIV for about 1?h reduces the infectious titre of the virus in large wax-moth larvae Galleria mellonella to 4.5 lg ID50/mL. The influence of the C60 concentration on its anti-viral activity was tested in the concentration range from 1 to 0.001?mg/mL. It has been found that C60 is able to inactivate the iridovirus even in low concentrations. Consequently, the findings of this work suggest that photoexcited C60 fullerenes can be successfully used for the inactivation of iridoviruses in biological systems. 相似文献