全文获取类型
收费全文 | 2544篇 |
免费 | 288篇 |
出版年
2022年 | 18篇 |
2021年 | 38篇 |
2020年 | 28篇 |
2019年 | 28篇 |
2018年 | 38篇 |
2017年 | 42篇 |
2016年 | 82篇 |
2015年 | 129篇 |
2014年 | 130篇 |
2013年 | 151篇 |
2012年 | 184篇 |
2011年 | 170篇 |
2010年 | 133篇 |
2009年 | 76篇 |
2008年 | 117篇 |
2007年 | 134篇 |
2006年 | 121篇 |
2005年 | 98篇 |
2004年 | 107篇 |
2003年 | 76篇 |
2002年 | 74篇 |
2001年 | 55篇 |
2000年 | 80篇 |
1999年 | 60篇 |
1998年 | 21篇 |
1997年 | 19篇 |
1996年 | 20篇 |
1995年 | 13篇 |
1994年 | 15篇 |
1993年 | 25篇 |
1992年 | 31篇 |
1991年 | 33篇 |
1990年 | 35篇 |
1989年 | 25篇 |
1988年 | 25篇 |
1987年 | 19篇 |
1986年 | 19篇 |
1985年 | 19篇 |
1984年 | 24篇 |
1983年 | 24篇 |
1982年 | 18篇 |
1981年 | 18篇 |
1979年 | 16篇 |
1978年 | 14篇 |
1977年 | 19篇 |
1974年 | 16篇 |
1973年 | 21篇 |
1972年 | 16篇 |
1969年 | 21篇 |
1968年 | 12篇 |
排序方式: 共有2832条查询结果,搜索用时 15 毫秒
71.
Marie Spohn Karolin Müller Carmen Hschen Carsten W. Mueller Sven Marhan 《Global Change Biology》2020,26(3):1926-1935
Dark, that is, nonphototrophic, microbial CO2 fixation occurs in a large range of soils. However, it is still not known whether dark microbial CO2 fixation substantially contributes to the C balance of soils and what factors control this process. Therefore, the objective of this study was to quantitate dark microbial CO2 fixation in temperate forest soils, to determine the relationship between the soil CO2 concentration and dark microbial CO2 fixation, and to estimate the relative contribution of different microbial groups to dark CO2 fixation. For this purpose, we conducted a 13C‐CO2 labeling experiment. We found that the rates of dark microbial CO2 fixation were positively correlated with the CO2 concentration in all soils. Dark microbial CO2 fixation amounted to up to 320 µg C kg?1 soil day?1 in the Ah horizon. The fixation rates were 2.8–8.9 times higher in the Ah horizon than in the Bw1 horizon. Although the rates of dark microbial fixation were small compared to the respiration rate (1.2%–3.9% of the respiration rate), our findings suggest that organic matter formed by microorganisms from CO2 contributes to the soil organic matter pool, especially given that microbial detritus is more stable in soil than plant detritus. Phospholipid fatty acid analyses indicated that CO2 was mostly fixed by gram‐positive bacteria, and not by fungi. In conclusion, our study shows that the dark microbial CO2 fixation rate in temperate forest soils increases in periods of high CO2 concentrations, that dark microbial CO2 fixation is mostly accomplished by gram‐positive bacteria, and that dark microbial CO2 fixation contributes to the formation of soil organic matter. 相似文献
72.
Victoria M. Stevens Scott W. Mueller Paul M. Reynolds Robert MacLaren Tyree H. Kiser 《Current fungal infection reports》2020,14(1):50-62
This article aimed to review animal models of antifungals and identifies human literature to assess if the extrapolation of results is reliable. Animal studies have helped identify area under the concentration curve to minimum inhibitory concentration ratio targets for new drugs and formulations such as isavuconazole and delayed-release posaconazole that have translated to successful outcomes in humans. Models have also been influential in the identification of possible combination therapies for the treatment of aspergillosis, such as voriconazole and echinocandins. However, challenges are endured with animal models when it comes to replicating the pharmacokinetics of humans which has been exemplified with the newest itraconazole formulation. Additionally, animal models have displayed a survival benefit with the use of iron chelators and amphotericin for mucormycosis which was not demonstrated in humans. Animal models have been a staple in the development and optimization of antifungal agents. They afford the ability to investigate uncommon diseases, such as invasive fungal infections, that would otherwise take years and many resources to complete. Although there are many benefits of animal models, there are also shortcomings. This is why the reliability of extrapolating data from animal models to humans is often scrutinized. 相似文献
73.
Noe Fernandez‐Pozo Fabian B. Haas Rabea Meyberg Kristian K. Ullrich Manuel Hiss Pierre‐Franois Perroud Sebastian Hanke Viktor Kratz Adrian F. Powell Eleanor F. Vesty Christopher G. Daum Matthew Zane Anna Lipzen Avinash Sreedasyam Jane Grimwood Juliet C. Coates Kerrie Barry Jeremy Schmutz Lukas A. Mueller Stefan A. Rensing 《The Plant journal : for cell and molecular biology》2020,102(1):165-177
Physcomitrella patens is a bryophyte model plant that is often used to study plant evolution and development. Its resources are of great importance for comparative genomics and evo‐devo approaches. However, expression data from Physcomitrella patens were so far generated using different gene annotation versions and three different platforms: CombiMatrix and NimbleGen expression microarrays and RNA sequencing. The currently available P. patens expression data are distributed across three tools with different visualization methods to access the data. Here, we introduce an interactive expression atlas, Physcomitrella Expression Atlas Tool (PEATmoss), that unifies publicly available expression data for P. patens and provides multiple visualization methods to query the data in a single web‐based tool. Moreover, PEATmoss includes 35 expression experiments not previously available in any other expression atlas. To facilitate gene expression queries across different gene annotation versions, and to access P. patens annotations and related resources, a lookup database and web tool linked to PEATmoss was implemented. PEATmoss can be accessed at https://peatmoss.online.uni-marburg.de 相似文献
74.
David Saleh Gang Wang Benedict Mueller Federico Rischawy Simon Kluters Joey Studts Jürgen Hubbuch 《Biotechnology progress》2021,37(1):e3081
Cation exchange chromatography (CEX) is an essential part of most monoclonal antibody (mAb) purification platforms. Process characterization and root cause investigation of chromatographic unit operations are performed using scale down models (SDM). SDM chromatography columns typically have the identical bed height as the respective manufacturing-scale, but a significantly reduced inner diameter. While SDMs enable process development demanding less material and time, their comparability to manufacturing-scale can be affected by variability in feed composition, mobile phase and resin properties, or dispersion effects depending on the chromatography system at hand. Mechanistic models can help to close gaps between scales and reduce experimental efforts compared to experimental SDM applications. In this study, a multicomponent steric mass-action (SMA) adsorption model was applied to the scale-up of a CEX polishing step. Based on chromatograms and elution pool data ranging from laboratory- to manufacturing-scale, the proposed modeling workflow enabled early identification of differences between scales, for example, system dispersion effects or ionic capacity variability. A multistage model qualification approach was introduced to measure the model quality and to understand the model's limitations across scales. The experimental SDM and the in silico model were qualified against large-scale data using the identical state of the art equivalence testing procedure. The mechanistic chromatography model avoided limitations of the SDM by capturing effects of bed height, loading density, feed composition, and mobile phase properties. The results demonstrate the applicability of mechanistic chromatography models as a possible alternative to conventional SDM approaches. 相似文献
75.
Megan K. Mueller 《应用发育科学》2013,17(1):5-16
Human-animal relationships are ubiquitous and diverse across the life span and may be especially salient among children and adolescents. However, there is little information regarding whether human-animal interaction (HAI) is actually linked to young people's positive development in normative, nontherapeutic settings. Therefore, the purpose of this study was to explore if and how HAI may be linked to positive youth development (PYD) using data from the 4-H Study of PYD. Results suggested that emotions and cognitions about animals were related to indices of positive development. The implications of these findings, and suggestions for new areas of inquiry regarding the role of HAI as an important developmental context, are discussed. 相似文献
76.
Global Analysis of Apicomplexan Protein S‐Acyl Transferases Reveals an Enzyme Essential for Invasion
Karine Frénal Chwen L. Tay Christina Mueller Ellen S. Bushell Yonggen Jia Arnault Graindorge Oliver Billker Julian C. Rayner Dominique Soldati‐Favre 《Traffic (Copenhagen, Denmark)》2013,14(8):895-911
The advent of techniques to study palmitoylation on a whole proteome scale has revealed that it is an important reversible modification that plays a role in regulating multiple biological processes. Palmitoylation can control the affinity of a protein for lipid membranes, which allows it to impact protein trafficking, stability, folding, signalling and interactions. The publication of the palmitome of the schizont stage of Plasmodium falciparum implicated a role for palmitoylation in host cell invasion, protein export and organelle biogenesis. However, nothing is known so far about the repertoire of protein S‐acyl transferases (PATs) that catalyse this modification in Apicomplexa. We undertook a comprehensive analysis of the repertoire of Asp‐His‐His‐Cys cysteine‐rich domain (DHHC‐CRD) PAT family in Toxoplasma gondii and Plasmodium berghei by assessing their localization and essentiality. Unlike functional redundancies reported in other eukaryotes, some apicomplexan‐specific DHHCs are essential for parasite growth, and several are targeted to organelles unique to this phylum. Of particular interest is DHHC7, which localizes to rhoptry organelles in all parasites tested, including the major human pathogen P. falciparum. TgDHHC7 interferes with the localization of the rhoptry palmitoylated protein TgARO and affects the apical positioning of the rhoptry organelles. This PAT has a major impact on T. gondii host cell invasion, but not on the parasite's ability to egress. 相似文献
77.
Sara Montanari Munazza Saeed Mareike Kn?bel YoonKyeong Kim Michela Troggio Mickael Malnoy Riccardo Velasco Paolo Fontana KyungHo Won Charles-Eric Durel Laure Perchepied Robert Schaffer Claudia Wiedow Vincent Bus Lester Brewer Susan E. Gardiner Ross N. Crowhurst David Chagné 《PloS one》2013,8(10)
We have used new generation sequencing (NGS) technologies to identify single nucleotide polymorphism (SNP) markers from three European pear (Pyrus communis L.) cultivars and subsequently developed a subset of 1096 pear SNPs into high throughput markers by combining them with the set of 7692 apple SNPs on the IRSC apple Infinium® II 8K array. We then evaluated this apple and pear Infinium® II 9K SNP array for large-scale genotyping in pear across several species, using both pear and apple SNPs. The segregating populations employed for array validation included a segregating population of European pear (‘Old Home’בLouise Bon Jersey’) and four interspecific breeding families derived from Asian (P. pyrifolia Nakai and P. bretschneideri Rehd.) and European pear pedigrees. In total, we mapped 857 polymorphic pear markers to construct the first SNP-based genetic maps for pear, comprising 78% of the total pear SNPs included in the array. In addition, 1031 SNP markers derived from apple (13% of the total apple SNPs included in the array) were polymorphic and were mapped in one or more of the pear populations. These results are the first to demonstrate SNP transferability across the genera Malus and Pyrus. Our construction of high density SNP-based and gene-based genetic maps in pear represents an important step towards the identification of chromosomal regions associated with a range of horticultural characters, such as pest and disease resistance, orchard yield and fruit quality. 相似文献
78.
Jessica L. Barrington-Trimis Susan Searles Nielsen Susan Preston-Martin W. James Gauderman Elizabeth A. Holly Federico M. Farin Beth A. Mueller Roberta McKean-Cowdin 《PloS one》2013,8(11)
Background
A recent meta-analysis suggested an association between exposure to paternal smoking during pregnancy and childhood brain tumor risk, but no studies have evaluated whether this association differs by polymorphisms in genes that metabolize tobacco-smoke chemicals.Methods
We assessed 9 functional polymorphisms in 6 genes that affect the metabolism of polycyclic aromatic hydrocarbons (PAH) to evaluate potential interactions with parental smoking during pregnancy in a population-based case-control study of childhood brain tumors. Cases (N = 202) were ≤10 years old, diagnosed from 1984–1991 and identified in three Surveillance, Epidemiology, and End Results (SEER) registries in the western U.S. Controls in the same regions (N = 286) were frequency matched by age, sex, and study center. DNA for genotyping was obtained from archived newborn dried blood spots.Results
We found positive interaction odds ratios (ORs) for both maternal and paternal smoking during pregnancy, EPHX1 H139R, and childhood brain tumors (P interaction = 0.02; 0.10), such that children with the high-risk (greater PAH activation) genotype were at a higher risk of brain tumors relative to children with the low-risk genotype when exposed to tobacco smoke during pregnancy. A dose-response pattern for paternal smoking was observed among children with the EPHX1 H139R high-risk genotype only (ORno exposure = 1.0; OR≤3 hours/day = 1.32, 95% CI: 0.52–3.34; OR>3hours/day = 3.18, 95% CI: 0.92–11.0; P trend = 0.07).Conclusion
Parental smoking during pregnancy may be a risk factor for childhood brain tumors among genetically susceptible children who more rapidly activate PAH in tobacco smoke. 相似文献79.
Cristian Koepfli Kathryn L. Colborn Benson Kiniboro Enmoore Lin Terence P. Speed Peter M. Siba Ingrid Felger Ivo Mueller 《PLoS neglected tropical diseases》2013,7(9)
Background
When both parasite species are co-endemic, Plasmodium vivax incidence peaks in younger children compared to P. falciparum. To identify differences in the number of blood stage infections of these species and its potential link to acquisition of immunity, we have estimated the molecular force of blood-stage infection of P. vivax (molFOB, i.e. the number of genetically distinct blood-stage infections over time), and compared it to previously reported values for P. falciparum.Methods
P. vivax molFOB was estimated by high resolution genotyping parasites in samples collected over 16 months in a cohort of 264 Papua New Guinean children living in an area highly endemic for P. falciparum and P. vivax. In this cohort, P. vivax episodes decreased three-fold over the age range of 1–4.5 years.Results
On average, children acquired 14.0 new P. vivax blood-stage clones/child/year-at-risk. While the incidence of clinical P. vivax illness was strongly associated with molFOB (incidence rate ratio (IRR) = 1.99, 95% confidence interval (CI95) [1.80, 2.19]), molFOB did not change with age. The incidence of P. vivax showed a faster decrease with age in children with high (IRR = 0.49, CI95 [0.38, 0.64] p<0.001) compared to those with low exposure (IRR = 0.63, CI95[0.43, 0.93] p = 0.02).Conclusion
P. vivax molFOB is considerably higher than P. falciparum molFOB (5.5 clones/child/year-at-risk). The high number of P. vivax clones that infect children in early childhood contribute to the rapid acquisition of immunity against clinical P. vivax malaria. 相似文献80.
Kelly Williamson Victoria Schneider Rachel A. Jordan John E. Mueller Michelle Henderson Pozzi Mary Bryk 《PloS one》2013,8(3)
In S. cerevisiae, the lysine methyltransferase Set1 is a member of the multiprotein complex COMPASS. Set1 catalyzes mono-, di- and trimethylation of the fourth residue, lysine 4, of histone H3 using methyl groups from S-adenosylmethionine, and requires a subset of COMPASS proteins for this activity. The methylation activity of COMPASS regulates gene expression and chromosome segregation in vivo. To improve understanding of the catalytic mechanism of Set1, single amino acid substitutions were made within the SET domain. These Set1 mutants were evaluated in vivo by determining the levels of K4-methylated H3, assaying the strength of gene silencing at the rDNA and using a genetic assessment of kinetochore function as a proxy for defects in Dam1 methylation. The findings indicate that no single conserved active site base is required for H3K4 methylation by Set1. Instead, our data suggest that a number of aromatic residues in the SET domain contribute to the formation of an active site that facilitates substrate binding and dictates product specificity. Further, the results suggest that the attributes of Set1 required for trimethylation of histone H3 are those required for Pol II gene silencing at the rDNA and kinetochore function. 相似文献