全文获取类型
收费全文 | 792篇 |
免费 | 80篇 |
出版年
2023年 | 9篇 |
2022年 | 18篇 |
2021年 | 38篇 |
2020年 | 12篇 |
2019年 | 13篇 |
2018年 | 25篇 |
2017年 | 22篇 |
2016年 | 23篇 |
2015年 | 31篇 |
2014年 | 35篇 |
2013年 | 54篇 |
2012年 | 60篇 |
2011年 | 50篇 |
2010年 | 31篇 |
2009年 | 31篇 |
2008年 | 35篇 |
2007年 | 46篇 |
2006年 | 40篇 |
2005年 | 29篇 |
2004年 | 29篇 |
2003年 | 29篇 |
2002年 | 37篇 |
2001年 | 14篇 |
2000年 | 6篇 |
1999年 | 9篇 |
1998年 | 5篇 |
1997年 | 5篇 |
1996年 | 7篇 |
1995年 | 7篇 |
1993年 | 4篇 |
1992年 | 4篇 |
1991年 | 7篇 |
1990年 | 6篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1986年 | 6篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 6篇 |
1980年 | 4篇 |
1978年 | 7篇 |
1977年 | 5篇 |
1976年 | 6篇 |
1975年 | 4篇 |
1971年 | 3篇 |
1970年 | 5篇 |
1969年 | 4篇 |
1966年 | 4篇 |
1965年 | 3篇 |
排序方式: 共有872条查询结果,搜索用时 403 毫秒
51.
Colleen Podmore Ian D. Hogg Gabrielle M. Drayton Barbara I. P. Barratt Ian A. W. Scott Robert G. Foottit 《New Zealand journal of zoology.》2019,46(2):107-123
Focussed searches were made across New Zealand between 2013 and 2016, for endemic aphids from the Schizaphis (Rhopalosiphina) genus, which is currently represented by two putative, undescribed species from the endemic host plants Aciphylla and Dracophyllum. Cytochrome c oxidase I (COI) gene sequences (48 in total) from the Schizaphis were analysed together with those from a broader collection of New Zealand endemic aphids that has been assembled since the year 2000. The bulk of the Schizaphis belonged to two clusters corresponding to the host plant genera. Two aphids from central North Island Dracophyllum represented a much diverged lineage without clear affiliations to other New Zealand Schizaphis. Inter-population variation in the New Zealand Schizaphis was high compared with that seen in international studies of Aphidinae and among populations of other endemic New Zealand Aphidina. Within Schizaphis from Dracophyllum, geography played an apparent role in genetic structuring, with populations from Taranaki (North Island) and especially Mt Lyford (South Island) being divergent from those on the South Island main divide. Two distinct lineages of Schizaphis, which co-occurred at some sites, were found on Aciphylla. Our sequence comparisons, including GMYC analyses, indicated up to five New Zealand Schizaphis lineages, and two newly discovered endemic Aphis species from the host plants Clematis and Hebe. 相似文献
52.
Different anteroposterior (AP) regions of the neural crest normally produce different cell types, both in vivo and in vitro. AP differences in neural crest cell fates appear to be specified in part by mechanisms that act prior to neural crest cell migration. We, therefore, examined the possibility that the fates of neural crest cells, like those of neural tube cells, can be regulated by interactions with Hensen's node. Using a transfilter co-culture system, we found that young (stage 3+ to 4) Hensen's node up-regulates the expression of two cranial-specific phenotypes (fibronectin and smooth muscle actin immunoreactivities) in mass cultures of trunk neural crest cells, and down-regulates the expression of a trunk-specific phenotype (melanin synthesis). The changes in phenotype produced by exposure to young Hensen's node were not accompanied by changes in the proliferation of either fibronectin immunoreactive cells or melanocytes. The capacity of Hensen's node to elicit changes in trunk neural crest cell phenotype decreased as the developmental age of the node increased and was lost by stage 6. In addition, old Hensen's node did not stimulate the expression of trunk-specific phenotypes in cranial neural crest cells, suggesting that cranial- and trunk-specific phenotypes are induced by different mechanisms. © 1996 John Wiley & Sons, Inc. 相似文献
53.
Lucas R. Struble Audrey L. Smith William E. Lutz Gabrielle Grubbs Satish Sagar Kenneth W. Bayles Prakash Radhakrishnan Surender Khurana Dalia ElGamal Gloria E. O. Borgstahl 《Protein science : a publication of the Protein Society》2022,31(5)
The COVID‐19 pandemic caused by SARS‐CoV‐2 infection has led to socio‐economic shutdowns and the loss of over 5 million lives worldwide. There is a need for the identification of therapeutic targets to treat COVID‐19. SARS‐CoV‐2 spike is a target of interest for the development of therapeutic targets. We developed a robust SARS‐CoV‐2 S spike expression and purification protocol from insect cells and studied four recombinant SARS‐CoV‐2 spike protein constructs based on the original SARS‐CoV‐2 sequence using a baculovirus expression system: a spike protein receptor‐binding domain that includes the SD1 domain (RBD) coupled to a fluorescent tag (S‐RBD‐eGFP), spike ectodomain coupled to a fluorescent tag (S‐Ecto‐eGFP), spike ectodomain with six proline mutations and a foldon domain (S‐Ecto‐HexaPro(+F)), and spike ectodomain with six proline mutations without the foldon domain (S‐Ecto‐HexaPro(‐F)). We tested the yield of purified protein expressed from the insect cell lines Spodoptera frugiperda (Sf9) and Trichoplusia ni (Tni) and compared it to previous research using mammalian cell lines to determine changes in protein yield. We demonstrated quick and inexpensive production of functional glycosylated spike protein of high purity capable of recognizing and binding to the angiotensin converting enzyme 2 (ACE2) receptor. To further confirm functionality, we demonstrate binding of eGFP fused construct of the spike ectodomain (S‐Ecto‐eGFP) to surface ACE2 receptors on lung epithelial cells by flow cytometry analysis and show that it can be decreased by means of receptor manipulation (blockade or downregulation). 相似文献
54.
Genomewide linkage searches for Mendelian disease loci can be efficiently conducted using high-density SNP genotyping arrays 总被引:5,自引:0,他引:5
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Sellick GS Longman C Tolmie J Newbury-Ecob R Geenhalgh L Hughes S Whiteford M Garrett C Houlston RS 《Nucleic acids research》2004,32(20):e164
Genomewide linkage searches aimed at identifying disease susceptibility loci are generally conducted using 300–400 microsatellite markers. Genotyping bi-allelic single nucleotide polymorphisms (SNPs) provides an alternative strategy. The availability of dense SNP maps coupled with recent technological developments in highly paralleled SNP genotyping makes it practical to now consider the use of these markers for whole-genome genetic linkage analyses. Here, we report the findings from three successful genomewide linkage analyses of families segregating autosomal recessively inherited neonatal diabetes, craniosynostosis and dominantly inherited renal dysplasia using the Affymetrix 10K SNP array. A single locus was identified for each disease state, two of which are novel. The performance of the SNP array, both in terms of efficiency and precision, indicates that such platforms will become the dominant technology for performing genomewide linkage searches. 相似文献
55.
56.
57.
Rieckhof GE Yoshihara M Guan Z Littleton JT 《The Journal of biological chemistry》2003,278(42):41099-41108
Voltage-gated calcium channels couple changes in membrane potential to neuronal functions regulated by calcium, including neurotransmitter release. Here we report that presynaptic N-type calcium channels not only control neurotransmitter release but also regulate synaptic growth at Drosophila neuromuscular junctions. In a screen for behavioral mutants that disrupt synaptic transmission, an allele of the N-type calcium channel locus (Dmca1A) was identified that caused synaptic undergrowth. The underlying molecular defect was identified as a neutralization of a charged residue in the third S4 voltage sensor. RNA interference reduction of N-type calcium channel expression also reduced synaptic growth. Hypomorphic mutations in syntaxin-1A or n-synaptobrevin, which also disrupt neurotransmitter release, did not affect synapse proliferation at the neuromuscular junction, suggesting calcium entry through presynaptic N-type calcium channels, not neurotransmitter release per se, is important for synaptic growth. The reduced synapse proliferation in Dmca1A mutants is not due to increased synapse retraction but instead reflects a role for calcium influx in synaptic growth mechanisms. These results suggest N-type channels participate in synaptic growth through signaling pathways that are distinct from those that mediate neurotransmitter release. Linking presynaptic voltage-gated calcium entry to downstream calcium-sensitive synaptic growth regulators provides an efficient activity-dependent mechanism for modifying synaptic strength. 相似文献
58.
Andersen C Maier E Kemmer G Blass J Hilpert AK Benz R Reidl J 《The Journal of biological chemistry》2003,278(27):24269-24276
Haemophilus influenzae has an absolute requirement for NAD (factor V) because it lacks all biosynthetic enzymes necessary for de novo synthesis of that cofactor. Therefore, growth in vitro requires the presence of NAD itself, NMN, or nicotinamide riboside (NR). To address uptake abilities of these compounds, we investigated outer membrane proteins. By analyzing ompP2 knockout mutants, we found that NAD and NMN uptake was prevented, whereas NR uptake was not. Through investigation of the properties of purified OmpP2 in artificial lipid membrane systems, the substrate specificity of OmpP2 for NAD and NMN was determined, with KS values of approximately 8 and 4mm, respectively, in 0.1 m KCl, whereas no interaction was detected for the nucleoside NR and other purine or pyrimidine nucleotide or nucleoside species. Based on our analysis, we assume that an intrinsic binding site within OmpP2 exists that facilitates diffusion of these compounds across the outer membrane, recognizing carbonyl and exposed phosphate groups. Because OmpP2 was formerly described as a general diffusion porin, an additional property of acting as a facilitator for nicotinamide-based nucleotide transport may have evolved to support and optimize utilization of the essential cofactor sources NAD and NMN in H. influenzae. 相似文献
59.
Siegel DH Ashton GH Penagos HG Lee JV Feiler HS Wilhelmsen KC South AP Smith FJ Prescott AR Wessagowit V Oyama N Akiyama M Al Aboud D Al Aboud K Al Githami A Al Hawsawi K Al Ismaily A Al-Suwaid R Atherton DJ Caputo R Fine JD Frieden IJ Fuchs E Haber RM Harada T Kitajima Y Mallory SB Ogawa H Sahin S Shimizu H Suga Y Tadini G Tsuchiya K Wiebe CB Wojnarowska F Zaghloul AB Hamada T Mallipeddi R Eady RA McLean WH McGrath JA Epstein EH 《American journal of human genetics》2003,73(1):174-187
Kindler syndrome is an autosomal recessive disorder characterized by neonatal blistering, sun sensitivity, atrophy, abnormal pigmentation, and fragility of the skin. Linkage and homozygosity analysis in an isolated Panamanian cohort and in additional inbred families mapped the gene to 20p12.3. Loss-of-function mutations were identified in the FLJ20116 gene (renamed “KIND1” [encoding kindlin-1]). Kindlin-1 is a human homolog of the Caenorhabditis elegans protein UNC-112, a membrane-associated structural/signaling protein that has been implicated in linking the actin cytoskeleton to the extracellular matrix (ECM). Thus, Kindler syndrome is, to our knowledge, the first skin fragility disorder caused by a defect in actin-ECM linkage, rather than keratin-ECM linkage. 相似文献
60.