全文获取类型
收费全文 | 3730篇 |
免费 | 265篇 |
专业分类
3995篇 |
出版年
2024年 | 4篇 |
2023年 | 31篇 |
2022年 | 53篇 |
2021年 | 96篇 |
2020年 | 64篇 |
2019年 | 82篇 |
2018年 | 113篇 |
2017年 | 103篇 |
2016年 | 136篇 |
2015年 | 240篇 |
2014年 | 232篇 |
2013年 | 300篇 |
2012年 | 361篇 |
2011年 | 335篇 |
2010年 | 213篇 |
2009年 | 186篇 |
2008年 | 221篇 |
2007年 | 190篇 |
2006年 | 161篇 |
2005年 | 153篇 |
2004年 | 152篇 |
2003年 | 112篇 |
2002年 | 83篇 |
2001年 | 32篇 |
2000年 | 39篇 |
1999年 | 40篇 |
1998年 | 24篇 |
1997年 | 18篇 |
1996年 | 11篇 |
1995年 | 5篇 |
1994年 | 16篇 |
1993年 | 13篇 |
1992年 | 16篇 |
1991年 | 11篇 |
1990年 | 15篇 |
1989年 | 11篇 |
1988年 | 12篇 |
1987年 | 15篇 |
1986年 | 6篇 |
1985年 | 12篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1979年 | 8篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1974年 | 4篇 |
1968年 | 3篇 |
1967年 | 4篇 |
排序方式: 共有3995条查询结果,搜索用时 15 毫秒
81.
N'Diaye A Chen GK Palmer CD Ge B Tayo B Mathias RA Ding J Nalls MA Adeyemo A Adoue V Ambrosone CB Atwood L Bandera EV Becker LC Berndt SI Bernstein L Blot WJ Boerwinkle E Britton A Casey G Chanock SJ Demerath E Deming SL Diver WR Fox C Harris TB Hernandez DG Hu JJ Ingles SA John EM Johnson C Keating B Kittles RA Kolonel LN Kritchevsky SB Le Marchand L Lohman K Liu J Millikan RC Murphy A Musani S Neslund-Dudas C North KE Nyante S Ogunniyi A Ostrander EA Papanicolaou G Patel S Pettaway CA 《PLoS genetics》2011,7(10):e1002298
Adult height is a classic polygenic trait of high heritability (h
2 ∼0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ∼10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10−12 and 2p14-rs4315565, P = 1.2×10−8). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10−4 for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits. 相似文献
82.
83.
Decay of mRNAs targeted by RISC requires XRN1, the Ski complex, and the exosome 总被引:8,自引:1,他引:8 下载免费PDF全文
RNA interference (RNAi) is a conserved RNA silencing pathway that leads to sequence-specific mRNA decay in response to the presence of double-stranded RNA (dsRNA). Long dsRNA molecules are first processed by Dicer into 21-22-nucleotide small interfering RNAs (siRNAs). The siRNAs are incorporated into a multimeric RNA-induced silencing complex (RISC) that cleaves mRNAs at a site determined by complementarity with the siRNAs. Following this initial endonucleolytic cleavage, the mRNA is degraded by a mechanism that is not completely understood. We investigated the decay pathway of mRNAs targeted by RISC in Drosophila cells. We show that 5' mRNA fragments generated by RISC cleavage are rapidly degraded from their 3' ends by the exosome, whereas the 3' fragments are degraded from their 5' ends by XRN1. Exosome-mediated decay of the 5' fragments requires the Drosophila homologs of yeast Ski2p, Ski3p, and Ski8p, suggesting that their role as regulators of exosome activity is conserved. Our findings indicate that mRNAs targeted by siRNAs are degraded from the ends generated by RISC cleavage, without undergoing decapping or deadenylation. 相似文献
84.
Elisa Damiani Can Ince Fiorenza Orlando Elisa Pierpaoli Oscar Cirioni Andrea Giacometti Federico Mocchegiani Paolo Pelaia Mauro Provinciali Abele Donati 《PloS one》2016,11(3)
Background
Sepsis-induced microcirculatory alterations contribute to tissue hypoxia and organ dysfunction. In addition to its plasma volume expanding activity, human serum albumin (HSA) has anti-oxidant and anti-inflammatory properties and may have a protective role in the microcirculation during sepsis. The concentration of HSA infused may influence these effects. We compared the microcirculatory effects of the infusion of 4% and 20% HSA in an experimental model of sepsis.Methods
Adult male Wistar rats were equipped with arterial and venous catheters and received an intravenous infusion of lipopolysaccharide (LPS, serotype O127:B8, 10 mg/kg over 30 minutes) or vehicle (SHAM, n = 6). Two hours later, endotoxemic animals were randomized to receive 10 mL/kg of either 4% HSA (LPS+4%HSA, n = 6), 20% HSA (LPS+20%HSA, n = 6) or 0.9% NaCl (LPS+0.9%NaCl, n = 6). No fluids were given to an additional 6 animals (LPS). Vessel density and perfusion were assessed in the skeletal muscle microcirculation with sidestream dark field videomicroscopy at baseline (t0), 2 hours after LPS injection (t1), after HSA infusion (t2) and 1 hour later (t3). The mean arterial pressure (MAP) and heart rate were recorded. Serum endothelin-1 was measured at t2.Results
MAP was stable over time in all groups. The microcirculatory parameters were significantly altered in endotoxemic animals at t1. The infusion of both 4% and 20% HSA similarly increased the perfused vessel density and blood flow velocity and decreased the flow heterogeneity to control values. Microvascular perfusion was preserved in the LPS+20%HSA group at t3, whereas alterations reappeared in the LPS+4%HSA group.Conclusions
In a rat model of normotensive endotoxemia, the infusion of 4% or 20% HSA produced a similar acute improvement in the microvascular perfusion in otherwise unresuscitated animals. 相似文献85.
Paula Zaghetto Almeida Josana Maria Messias Marita Gimenez Pereira Vanessa Elisa Pinheiro Lummy Maria Oliveira Monteiro Paulo Ricardo Heinen 《Biocatalysis and Biotransformation》2018,36(5):389-395
Starch has great importance in human diet, since it is a heteropolymer of plants, mainly found in roots, as potato, cassava and arrowroots. This carbohydrate is composed by a highly-branched chain: amylopectin; and a linear chain: amylose. The proportion between the chains varies according to the botanical source. Starch hydrolysis is catalyzed by enzymes of the amilolytic system, named amylases. Among the various enzymes of this system, the glucoamylases (EC 3.2.1.3 glucan 1,4-alpha-glucosidases) are the majority because they hydrolyze the glycosidic linkages at the end of starch chains releasing glucose monomers. In this work, a glucoamylase secreted in the culture medium, by the ascomycete Aspergillus brasiliensis, was immobilized in Dietilaminoetil Sepharose-Polyethylene Glycol (DEAE-PEG), since immobilized biocatalysts are more stable in long periods of hydrolysis, and can be recovered from the final product and reused for several cycles. Glucoamylase immobilization has shown great thermal stability improvement over the soluble enzyme, reaching 66% more activity after 6?h at 60?°C, and 68% of the activity after 10 hydrolysis cycles. A simplex centroid experimental mixture design was applied as a tool to characterize the affinity of the immobilized enzyme for different starchy substrates. In assays containing several proportions of amylose, amylopectin and starch, the glucoamylase from A. brasiliensis mainly hydrolyzed the amylopectin chains, showing to have preference by branched substrates. 相似文献
86.
Giorgia Letizia Marcone Elisa Binda Francesca Berini Flavia Marinelli 《Biotechnology advances》2018,36(2):534-554
Glycopeptide antibiotics are drugs of last resort for treating severe infections caused by multi-drug resistant Gram-positive pathogens. First-generation glycopeptides (vancomycin and teicoplanin) are produced by soil-dwelling actinomycetes. Second-generation glycopeptides (dalbavancin, oritavancin, and telavancin) are semi-synthetic derivatives of the progenitor natural products. Herein, we cover past and present biotechnological approaches for searching for and producing old and new glycopeptide antibiotics. We review the strategies adopted to increase microbial production (from classical strain improvement to rational genetic engineering), and the recent progress in genome mining, chemoenzymatic derivatization, and combinatorial biosynthesis for expanding glycopeptide chemical diversity and tackling the never-ceasing evolution of antibiotic resistance. 相似文献
87.
88.
Elisa Garzo Mercedes Fernández‐Pascual Cesar Morcillo Alberto Fereres M. Luisa Gómez‐Guillamón W. Fred Tjallingii 《Insect Science》2018,25(4):631-642
Resistance of the melon line TGR‐1551 to the aphid Aphis gossypii is based on preventing aphids from ingesting phloem sap. In electrical penetration graphs (EPGs), this resistance has been characterized with A. gossypii showing unusually long phloem salivation periods (waveform E1) mostly followed by pathway activities (waveform C) or if followed by phloem ingestion (waveform E2), ingestion was not sustained for more than 10 min. Stylectomy with aphids on susceptible and resistant plants was performed during EPG recording while the stylet tips were phloem inserted. This was followed by dissection of the penetrated leaf section, plant tissue fixation, resin embedding, and ultrathin sectioning for transmission electron microscopic observation in order to study the resistance mechanism in the TGR. The most obvious aspect appeared to be the coagulation of phloem proteins inside the stylet canals and the punctured sieve elements. Stylets of 5 aphids per genotype were amputated during sieve element (SE) salivation (E1) and SE ingestion (E2). Cross‐sections of stylet bundles in susceptible melon plants showed that the contents of the stylet canals were totally clear and also, no coagulated phloem proteins occurred in their punctured sieve elements. In contrast, electron‐dense coagulations were found in both locations in the resistant plants. Due to calcium binding, aphid saliva has been hypothesized to play an essential role in preventing/suppressing such coagulations that cause occlusion of sieves plate and in the food canal of the aphid's stylets. Doubts about this role of E1 salivation are discussed on the basis of our results. 相似文献
89.
90.
African swine fever virus DNA sediments in neutral sucrose density gradients as a single component with a sedimentation coefficient of 60S. In alkaline sucrose density gradients, this material shows two components with sedimentation coefficients of 85S and 95S, respectively. The sedimentation rate value of alkali-denatured virus DNA in neutral sucrose density gradients and the renaturation velocity of denatured DNA show that is reassociated much faster than expected from its genetic complexity. This behavior is compatible with the existence of interstrand cross-links in the molecule. We also present results which suggest that there are only a few such cross-links per molecule, that they are sensitive to S1 nuclease digestion, and that they are probably located next to the ends of the DNA. 相似文献