全文获取类型
收费全文 | 15798篇 |
免费 | 1508篇 |
国内免费 | 5篇 |
出版年
2023年 | 81篇 |
2022年 | 203篇 |
2021年 | 437篇 |
2020年 | 271篇 |
2019年 | 298篇 |
2018年 | 350篇 |
2017年 | 307篇 |
2016年 | 493篇 |
2015年 | 852篇 |
2014年 | 921篇 |
2013年 | 1012篇 |
2012年 | 1349篇 |
2011年 | 1427篇 |
2010年 | 890篇 |
2009年 | 745篇 |
2008年 | 971篇 |
2007年 | 965篇 |
2006年 | 904篇 |
2005年 | 736篇 |
2004年 | 801篇 |
2003年 | 701篇 |
2002年 | 689篇 |
2001年 | 147篇 |
2000年 | 93篇 |
1999年 | 129篇 |
1998年 | 157篇 |
1997年 | 90篇 |
1996年 | 81篇 |
1995年 | 84篇 |
1994年 | 84篇 |
1993年 | 103篇 |
1992年 | 67篇 |
1991年 | 65篇 |
1990年 | 55篇 |
1989年 | 46篇 |
1988年 | 45篇 |
1987年 | 44篇 |
1986年 | 32篇 |
1985年 | 44篇 |
1984年 | 45篇 |
1983年 | 33篇 |
1982年 | 52篇 |
1981年 | 45篇 |
1980年 | 38篇 |
1979年 | 31篇 |
1978年 | 35篇 |
1977年 | 25篇 |
1976年 | 25篇 |
1975年 | 18篇 |
1974年 | 24篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
121.
The endoplasmic reticulum (ER) membrane protein complex (EMC) is essential for the insertion of a wide variety of transmembrane proteins into the plasma membrane across cell types. Each EMC is composed of Emc1-7, Emc10, and either Emc8 or Emc9. Recent human genetics studies have implicated variants in EMC genes as the basis for a group of human congenital diseases. The patient phenotypes are varied but appear to affect a subset of tissues more prominently than others. Namely, craniofacial development seems to be commonly affected. We previously developed an array of assays in Xenopus tropicalis to assess the effects of emc1 depletion on the neural crest, craniofacial cartilage, and neuromuscular function. We sought to extend this approach to additional EMC components identified in patients with congenital malformations. Through this approach, we determine that EMC9 and EMC10 are important for neural crest development and the development of craniofacial structures. The phenotypes observed in patients and our Xenopus model phenotypes similar to EMC1 loss of function likely due to a similar mechanism of dysfunction in transmembrane protein topogenesis. 相似文献
122.
Jonathan Lightner Gregory Pearce Clarence A. Ryan John Browse 《Molecular genetics and genomics : MGG》1993,241(5-6):595-601
As a first step towards developing a genetic system for investigating signaling processes in plants, we have developed a screen for signaling mutants deficient in a wound response. We have isolated two mutants of tomato that lack detectable production of proteinase inhibitors induced systemically in leaves by wounding. The mutants are deficient in the induction of both proteinase Inhibitor I and proteinase Inhibitor II but can be induced to respond at near wild-type levels by methyl jasmonate, a known elicitor of inhibitor production in tomato. While completely deficient in systemic production of proteinase inhibitors, both mutants produce some proteinase inhibitor in wounded leaves. This evidence suggests the existence of two signaling pathways, one local and one systemic, that regulate the induction of proteinase inhibitor snythesis in response to wounding. 相似文献
123.
124.
Jonathan D. G. Jones David A. Jones Gerard J. Bishop Kate Harrison Bernard J. Carroll Steven R. Scofield 《Transgenic research》1993,2(2):63-78
Cell-autonomous genes have been used to monitor the excision of both endogenous transposons in maize andAntirrhinum, and transposons introduced into transgenic plants. In tobacco andArabidopsis, the streptomycin phosphotransferase (SPT) gene reveals somatic excision of the maize transposonActivator (Ac) as green sectors on a white background in cotyledons of seedlings germinated in the presence of streptomycin. Cotyledons of tomato seedlings germinated on streptomycin-containing medium do not bleach, suggesting that a different assay for transposon excision in tomato is desirable. We have tested the use of the spectinomycin resistance (SPEC) gene (aadA) and a Basta resistance (BAR) gene (phosphinothricin acetyltransferase, or PAT) for monitoring somatic excision ofAc in tobacco and tomato. Both genetic and molecular studies demonstrate that genotypically variegated individuals that carry clones of cells from whichAc orDs have excised from either SPEC or BAR genes, can be phenotypically completely resistant to the corresponding antibiotic. This demonstrates that these genes act non-cell-autonomously, in contrast to the SPT gene in tobacco. Possible reasons for this difference are discussed. 相似文献
125.
126.
A rapid method for extraction of cotton (Gossypium spp.) genomic DNA suitable for RFLP or PCR analysis 总被引:13,自引:0,他引:13
Andrew H. Paterson Curt L. Brubaker Jonathan F. Wendel 《Plant Molecular Biology Reporter》1993,11(2):122-127
Extraction of high-quality genomic DNA fromGossypium (cotton) species is difficult due to high levels of polysaccharide, oxidizable quinones, and other interfering substances.
We describe a procedure that consistently permits isolation of cotton genomic DNA of satisfactory size and quality for RFLP
and PCR analysis, as well as for most routine cloning applications. Several antioxidants, phenol-binding reagents, and phenol
oxidase inhibitors are used throughout the procedure, and most polysaccharides are eliminated early in the procedure by isolation
of nuclei. 相似文献
127.
Jonathan Reizer Antonio H. Romano Josef Deutscher 《Journal of cellular biochemistry》1993,51(1):19-24
HPr of the Gram-positive bacterial phosphotransferase system (PTS) can be phosphorylated by an ATP-dependent protein kinase on a serine residue or by PEP-dependent Enzyme I on a histidyl residue. Both phosphorylation events appear to influence the metabolism of non-PTS carbon sources. Catabolite repression of the gluconate (gnt) operon of B. subtilis appears to be regulated by the former phosphorylation event, while glycerol kinase appears to be regulated by the latter phosphorylation reaction. The extent of our understanding of these processes will be described. © 1993 Wiley-Liss, Inc. 相似文献
128.
Helen E. O'connor David R. Stevens Stuart V. Ruffle Jonathan H. A. Nugent Saul Purton 《Plant Molecular Biology Reporter》1993,11(3):207-211
The isolation of chloroplast DNA fromChlamydomonas reinhardtii requires the efficient separation of this AT-rich genome from the GC-rich nuclear genome by density-gradient centrifugation.
We describe a simple and efficient method for separating these DNA fractions by using a sodium iodide gradient in combination
with the DNA-binding dye, bisbenzimide. The yield of chloroplast DNA is close to the theoretical maximum and the DNA is suitable
for restriction enzyme analysis and cloning. This method is applicable to the isolation of AT-rich plastid genomes from other
organisms and may be appropriate as a general method for separating species of DNA that differ in their AT/GC ratios.
An erratum to this article is available at . 相似文献
129.
Antigenic variation of pilin regulates adhesion of Neisseria meningitidis to human epithelial cells 总被引:20,自引:9,他引:11
Xavier Nassif Jonathan Lowy Paula Stenberg Peadar O'Gaora Amir Ganji Magdalene So 《Molecular microbiology》1993,8(4):719-725
Pili have been shown to play an essential role in the adhesion of Neisseria meningitidis to epithelial cells. However, among piliated strains, both inter- and intrastrain variability exist with respect to their degree of adhesion to epithelial cells in vitro (Virji et al., 1992). This suggests that factors other than the presence of pili per se are involved in this process. The N. meningitidis pilin subunit undergoes extensive antigenic variation. Piliated low- and high-adhesive derivatives of the same N. meningitidis strain were selected and the nucleotide sequence of the pilin gene expressed in each was determined. The highly adhesive derivatives had the same pilin sequence. The alleles encoding the pilin subunit of the low-adhesive derivatives were completely different from the one found in the high-adhesive isolates. Using polyclonal antibodies raised against one hyperadhesive variant, it was confirmed that the low-adhesive piliated derivatives expressed pilin variants antigenically different from the highly adhesive strains. The role of antigenic variation in the adhesive process of N. meningitidis was confirmed by performing allelic exchanges of the pilE locus between low-and high-adhesive isolates. Antigenic variation has been considered a means by which virulent bacteria evade the host immune system. This work provides genetic proof that a bacterial pathogen, N. meningitidis, can use antigenic variation to modulate their degree of virulence. 相似文献
130.
García-Machorro Jazmin Mirzaeicheshmeh Elaheh Fragoso-Vázquez Manuel Jonathan Bello Martiniano Méndez-Luna David León-Cardona Alám Correa-Basurto José 《化学与生物多样性》2023,20(7):e202201077
Antiviral resistance has turned into a world concern nowadays. Influenza A H1N1 emerged as a problem at the world level due to the neuraminidase (NA) mutations. The NA mutants conferred resistance to oseltamivir and zanamivir. Several efforts were conducted to develop better anti-influenza A H1N1 drugs. Our research group combined in silico methods to create a compound derived from oseltamivir to be tested in vitro against influenza A H1N1. Here we show the results of a new compound derived from oseltamivir but with specific chemical modifications, with significant affinity either on NA (in silico and in vitro assays) or HA (in silico) from influenza A H1N1 strain. We include docking and molecular dynamics (MD) simulations of the oseltamivir derivative at the binding site onto NA and HA of influenza A H1N1. Additionally, the biological experimental results show that oseltamivir derivative decreases the lytic-plaque formation on viral susceptibility assays, and it does not show cytotoxicity. Finally, oseltamivir derivative assayed on viral NA showed a concentration-dependent inhibition behavior at nM, depicting a high affinity of the compound for the enzyme, corroborated with the MD simulations results, placing our designed oseltamivir derivative as a potential antiviral against influenza A H1N1. 相似文献