全文获取类型
收费全文 | 735篇 |
免费 | 61篇 |
国内免费 | 9篇 |
出版年
2024年 | 2篇 |
2023年 | 5篇 |
2022年 | 11篇 |
2021年 | 16篇 |
2020年 | 20篇 |
2019年 | 21篇 |
2018年 | 25篇 |
2017年 | 26篇 |
2016年 | 31篇 |
2015年 | 45篇 |
2014年 | 54篇 |
2013年 | 58篇 |
2012年 | 57篇 |
2011年 | 51篇 |
2010年 | 37篇 |
2009年 | 35篇 |
2008年 | 28篇 |
2007年 | 35篇 |
2006年 | 32篇 |
2005年 | 22篇 |
2004年 | 21篇 |
2003年 | 15篇 |
2002年 | 18篇 |
2001年 | 14篇 |
2000年 | 15篇 |
1999年 | 10篇 |
1998年 | 11篇 |
1997年 | 8篇 |
1996年 | 8篇 |
1995年 | 3篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 6篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 2篇 |
1973年 | 3篇 |
1971年 | 1篇 |
1955年 | 1篇 |
1954年 | 2篇 |
排序方式: 共有805条查询结果,搜索用时 187 毫秒
1.
Hardies SC; Martin SL; Voliva CF; Hutchison CA d; Edgell MH 《Molecular biology and evolution》1986,3(2):109-125
2.
Abstract: The relationship between elevations in intracellular free Ca2+ concentration ([Ca2+]i) by different mechanisms and tyrosine hydroxylase (TH) gene expression was examined. Depolarization by an elevated K+ concentration triggered rapid and sustained increases in [Ca2+]i from a basal level of ~50 to 110–150 nM and three- to fourfold elevations in TH mRNA levels, requiring extracellular calcium but not inositol 1,4,5-trisphosphate (IP3). On the other hand, bradykinin or thapsigargin, both of which induce release of intracellular calcium stores via IP3 or inhibition of Ca2+-ATPase, rapidly elevated [Ca2+]i to >200 nM and increased TH gene expression (three-to fivefold). Confocal imaging showed that the elevations in [Ca2+]i in each case occurred throughout the cyto- and nucleoplasm. The initial rise in [Ca2+]i due to either bradykinin or thapsigargin, which did not require extracellular calcium, was sufficient to initiate the events leading to increased TH expression. Consistent with this, the effects of bradykinin on TH expression were inhibited by 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid or 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester which chelates or inhibits the release of intracellular calcium, respectively. Bradykinin required a rise in [Ca2+]i for <10 min, as opposed to 10–30 min for depolarization to increase TH mRNA levels. These results demonstrate that although each of these treatments increased TH gene expression by raising [Ca2+]i, there are important differences among them in terms of the magnitude of elevated [Ca2+]i, requirements for extracellular calcium or release of intracellular calcium stores, and duration of elevated [Ca2+]i, indicating the involvement of different calcium signaling pathways leading to regulation of TH gene expression. 相似文献
3.
Valentina Sora Adrian Otamendi Laspiur Kristine Degn Matteo Arnaudi Mattia Utichi Ludovica Beltrame Dayana De Menezes Matteo Orlandi Ulrik Kristoffer Stoltze Olga Rigina Peter Wad Sackett Karin Wadt Kjeld Schmiegelow Matteo Tiberti Elena Papaleo 《Protein science : a publication of the Protein Society》2023,32(1):e4527
Reliable prediction of free energy changes upon amino acid substitutions (ΔΔGs) is crucial to investigate their impact on protein stability and protein–protein interaction. Advances in experimental mutational scans allow high-throughput studies thanks to multiplex techniques. On the other hand, genomics initiatives provide a large amount of data on disease-related variants that can benefit from analyses with structure-based methods. Therefore, the computational field should keep the same pace and provide new tools for fast and accurate high-throughput ΔΔG calculations. In this context, the Rosetta modeling suite implements effective approaches to predict folding/unfolding ΔΔGs in a protein monomer upon amino acid substitutions and calculate the changes in binding free energy in protein complexes. However, their application can be challenging to users without extensive experience with Rosetta. Furthermore, Rosetta protocols for ΔΔG prediction are designed considering one variant at a time, making the setup of high-throughput screenings cumbersome. For these reasons, we devised RosettaDDGPrediction, a customizable Python wrapper designed to run free energy calculations on a set of amino acid substitutions using Rosetta protocols with little intervention from the user. Moreover, RosettaDDGPrediction assists with checking completed runs and aggregates raw data for multiple variants, as well as generates publication-ready graphics. We showed the potential of the tool in four case studies, including variants of uncertain significance in childhood cancer, proteins with known experimental unfolding ΔΔGs values, interactions between target proteins and disordered motifs, and phosphomimetics. RosettaDDGPrediction is available, free of charge and under GNU General Public License v3.0, at https://github.com/ELELAB/RosettaDDGPrediction . 相似文献
4.
A major difference between the divergence patterns within the lines-1 families in mice and voles 总被引:3,自引:0,他引:3
Vanlerberghe F; Bonhomme F; Hutchison CA d; Edgell MH 《Molecular biology and evolution》1993,10(4):719-731
L1 retroposons are represented in mice by subfamilies of interspersed
sequences of varied abundance. Previous analyses have indicated that
subfamilies are generated by duplicative transposition of a small number of
members of the L1 family, the progeny of which then become a major
component of the murine L1 population, and are not due to any active
processes generating homology within preexisting groups of elements in a
particular species. In mice, more than a third of the L1 elements belong to
a clade that became active approximately 5 Mya and whose elements are >
or = 95% identical. We have collected sequence information from 13 L1
elements isolated from two species of voles (Rodentia: Microtinae: Microtus
and Arvicola) and have found that divergence within the vole L1 population
is quite different from that in mice, in that there is no abundant
subfamily of homologous elements. Individual L1 elements from voles are
very divergent from one another and belong to a clade that began a period
of elevated duplicative transposition approximately 13 Mya. Sequence
analyses of portions of these divergent L1 elements (approximately 250 bp
each) gave no evidence for concerted evolution having acted on the vole L1
elements since the split of the two vole lineages approximately 3.5 Mya;
that is, the observed interspecific divergence (6.7%-24.7%) is not larger
than the intraspecific divergence (7.9%-27.2%), and phylogenetic analyses
showed no clustering into Arvicola and Microtus clades.
相似文献
5.
Molecular phylogeny and divergence times of drosophilid species 总被引:32,自引:15,他引:17
The phylogenetic relationships and divergence times of 39 drosophilid
species were studied by using the coding region of the Adh gene. Four
genera--Scaptodrosophila, Zaprionus, Drosophila, and Scaptomyza (from
Hawaii)--and three Drosophila subgenera--Drosophila, Engiscaptomyza, and
Sophophora--were included. After conducting statistical analyses of the
nucleotide sequences of the Adh, Adhr (Adh-related gene), and nuclear rRNA
genes and a 905-bp segment of mitochondrial DNA, we used Scaptodrosophila
as the outgroup. The phylogenetic tree obtained showed that the first major
division of drosophilid species occurs between subgenus Sophophora (genus
Drosophila) and the group including subgenera Drosophila and Engiscaptomyza
plus the genera Zaprionus and Scaptomyza. Subgenus Sophophora is then
divided into D. willistoni and the clade of D. obscura and D. melanogaster
species groups. In the other major drosophilid group, Zaprionus first
separates from the other species, and then D. immigrans leaves the
remaining group of species. This remaining group then splits into the D.
repleta group and the Hawaiian drosophilid cluster (Hawaiian Drosophila,
Engiscaptomyza, and Scaptomyza). Engiscaptomyza and Scaptomyza are tightly
clustered. Each of the D. repleta, D. obscura, and D. melanogaster groups
is monophyletic. The splitting of subgenera Drosophila and Sophophora
apparently occurred about 40 Mya, whereas the D. repleta group and the
Hawaiian drosophilid cluster separated about 32 Mya. By contrast, the
splitting of Engiscaptomyza and Scaptomyza occurred only about 11 Mya,
suggesting that Scaptomyza experienced a rapid morphological evolution. The
D. obscura and D. melanogaster groups apparently diverged about 25 Mya.
Many of the D. repleta group species studied here have two functional Adh
genes (Adh-1 and Adh-2), and these duplicated genes can be explained by two
duplication events.
相似文献
6.
Presence of Epstein-Barr virus receptors, but absence of virus penetration, in cells of an Epstein-Barr virus genome-negative human lymphoblastoid T line (Molt 4). 总被引:5,自引:0,他引:5
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
This paper reports a unique type of interaction of Epstein-Barr virus (EBV) with an EBV receptor-positive, genome-negative human lymphoid T cell line (Molt 4), which can be summarized as follows. Although Molt 4 cells express receptors for EBV, they appear to block the penetration of this virus. These observations are derived from combined studies with immunofluorescence and electron microscopy. It is possible that T cell lines bearing receptors for EBV may express such a control on virus penetration. 相似文献
7.
Sulfate reduction and S-oxidation in a moorland pool sediment 总被引:3,自引:2,他引:1
In an oligotrophic moorland pool in The Netherlands, S cycling near the sediment/water boundary was investigated by measuring (1) SO4
2– reduction rates in the sediment, (2) depletion of SO4
2– in the overlying water column and (3) release of35S from the sediment into the water column. Two locations differing in sediment type (highly organic and sandy) were compared, with respect to reduction rates and depletion of SO4
2– in the overlying water.Sulfate reduction rates in sediments of an oligotrophic moorland pool were estimated by diagenetic modelling and whole core35SO4
2– injection. Rates of SO4
2– consumption in the overlying water were estimated by changes in SO4
2– concentration over time in in situ enclosures. Reduction rates ranged from 0.27–11.2 mmol m–2 d–1. Rates of SO4
2– uptake from the enclosed water column varied from –0.5, –0.3 mmol m–2 d–1 (November) to 0.43–1.81 mmol m–2 d–1 (July, August and April). Maximum rates of oxidation to SO4
2– in July 1990 estimated by combination of SO4
2– reduction rates and rates of in situ SO4
2– uptake in the enclosed water column were 10.3 and 10.5 mmol m–2 d–1 at an organic rich and at a sandy site respectively.Experiments with35S2– and35SO4
2– tracer suggested (1) a rapid formation of organically bound S from dissimilatory reduced SO4
2– and (2) the presence of mainly non SO4
2–-S derived from reduced S transported from the sediment into the overlying water. A35S2– tracer experiment showed that about 7% of35S2– injected at 1 cm depth in a sediment core was recovered in the overlying water column.Sulfate reduction rates in sediments with higher volumetric mass fraction of organic matter did not significantly differ from those in sediments with a lower mass fraction of organic matter.Corresponding author 相似文献
8.
Yeast hexokinase A(ATP:D-hexose 6-phosphotransferase) is inactivated when incubated in the presence of xylose and ATPMg, or in the presence of D-lyxose in a reaction medium in which ATPMg is being continuously regenerated (phosphoenolpyruvate and pyruvate kinase). The inactivation is due to the phorphorylation of the protein. A linear relationship was observed between the inactivation and the incorporation of 32P from [gamma-32P] ATP. All hexokinase and ATPase activity of the enzyme is lost when one phosphoryl group is incorporated per enzyme subunit (molecular weight 51,000). The phosphoryl group is covalently bound by a ester linkage with a serine residue of the protein. 相似文献
9.
JOSEP PIÑOL XAVIER ESPADALER NÚRIA CAÑELLAS JORDI MARTÍNEZ‐VILALTA JOSÉ A. BARRIENTOS DANIEL SOL 《Ecological Entomology》2010,35(3):367-376
1. Predation‐exclusion experiments have highlighted that top‐down control is pervasive in terrestrial communities, but most of these experiments are simplistic in that they only excluded a single group of predators and the effect of removal was evaluated on a few species from the community. The main goal of our study was to experimentally establish the relative effects of ants and birds on the same arthropod assemblage of canopy trees. 2. We conducted 1‐year long manipulative experiments in an organic citrus grove intended to quantify the independent effects of bird and ant predators on the abundance of arthropods. Birds were excluded with plastic nets whereas ants were excluded with sticky barriers on the trunks. The sticky barrier also excluded other ground dwelling insects, like the European earwig Forficula auricularia L. 3. Both the exclusion of ants and birds affected the arthropod community of the citrus canopies, but the exclusion of ants was far more important than the exclusion of birds. Indeed, almost all groups of arthropods had higher abundance in ant‐excluded than in control trees, whereas only dermapterans were more abundant in bird‐excluded than in control trees. A more detailed analysis conducted on spiders also showed that the effect of ant exclusion was limited to a few families rather than being widespread over the entire diverse spectrum of spiders. 4. Our results suggest that the relative importance of vertebrate and invertebrate predators in regulating arthropod populations largely depends on the nature of the predator–prey system. 相似文献
10.
Fred Bernardes Filho Jaci Maria Santana Regina Coeli Palma de Almeida Glauber Voltan Natlia Aparecida de Paula Marcel Nani Leite Claudia Maria Lincoln Silva Camila Tormena Lean Basoli Joelma Menezes Moises Batista da Silva John Stewart Spencer Wilson Marques Jr Norma Tiraboschi Foss Marco Andrey Cipriani Frade 《PLoS neglected tropical diseases》2020,14(12)
BackgroundThis study evaluates an active search strategy for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzing the clinical, immunoepidemiological and follow-up aspects for individuals living in a prison population.MethodsA cross-sectional study based on a questionnaire posing 14 questions about leprosy symptoms and signs that was distributed to 1,400 prisoners. This was followed by dermatoneurological examination, anti-PGL-I serology and RLEP-PCR. Those without leprosy were placed in the Non-leprosy Group (NLG, n = 1,216) and those diagnosed with clinical symptoms of leprosy were placed in the Leprosy Group (LG, n = 34).FindingsIn total, 896 LSQ were returned (64%), and 187 (20.9%) of the responses were deemed as positive for signs/symptoms, answering 2.7 questions on average. Clinically, 1,250 (89.3%) of the prisoners were evaluated resulting in the diagnosis of 34 new cases (LG), based on well-accepted clinical signs and symptoms, a new case detection rate of 2.7% within this population, while the NLG were comprised of 1,216 individuals. The confinement time medians were 39 months in the LG while it was 36 months in the NLG (p>0.05). The 31 leprosy cases who responded to the questionnaire (LSQ+) had an average of 1.5 responses. The symptoms “anesthetized skin area” and “pain in nerves” were most commonly mentioned in the LG while “tingling, numbness in the hands/feet”, “sensation of pricks and needles”, “pain in nerves” and “spots on the skin” responses were found in more than 30% of questionnaires in the NLG. Clinically, 88.2% had dysesthetic macular skin lesions and 97.1% presented some peripheral nerve impairment, 71.9% with some degree of disability. All cases were multibacillary, confirming a late diagnosis. Anti-PGL-I results in the LG were higher than in the NLG (p<0.0001), while the RLEP-PCR was positive in 11.8% of the patients.InterpretationOur findings within the penitentiary demonstrated a hidden prevalence of leprosy, although the individuals diagnosed were likely infected while living in their former communities and not as a result of exposure in the prison. The LSQ proved to be an important screening tool to help identify leprosy cases in prisons. 相似文献