全文获取类型
收费全文 | 644篇 |
免费 | 51篇 |
专业分类
695篇 |
出版年
2023年 | 4篇 |
2022年 | 6篇 |
2021年 | 15篇 |
2020年 | 8篇 |
2019年 | 12篇 |
2018年 | 17篇 |
2017年 | 14篇 |
2016年 | 23篇 |
2015年 | 32篇 |
2014年 | 40篇 |
2013年 | 44篇 |
2012年 | 53篇 |
2011年 | 35篇 |
2010年 | 32篇 |
2009年 | 26篇 |
2008年 | 36篇 |
2007年 | 39篇 |
2006年 | 26篇 |
2005年 | 34篇 |
2004年 | 42篇 |
2003年 | 31篇 |
2002年 | 31篇 |
2001年 | 8篇 |
2000年 | 11篇 |
1999年 | 13篇 |
1998年 | 8篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 7篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1973年 | 2篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有695条查询结果,搜索用时 15 毫秒
31.
Bruna Tedeschi Patrizia Vernole M.Lucia Sanna Benedetto Nicoletti 《Human genetics》1992,89(5):543-547
Summary Chromosome fragile sites are inducible by aphidicolin in cultured human lymphocytes. To assess the frequency and distribution of these common fragile sites in the general population, a cytogenetic survey was performed on 126 subjects, 59 males and 67 females, whose age ranged from 1 day to 72 years. Common fragile sites, induced by aphidicolin, were widespread and showed a remarkably different sensitivity among individuals; age influenced the overall frequency of fragile sites. Moreover, both age and sex seemed to modulate the expression of specific fragile sites. In our population, the most common fragile sites were: 3p14, 16q23, Xp22, 6q26, 1p31, 4q31, 1p22, 7q22, 2q33, 3q27, 2q31, 7q32, 14q24, 10q22, 5q31, 2q37, 6p21. 相似文献
32.
Nuno Cerca Silvia Martins Sanna Sillankorva Kimberly K. Jefferson Gerald B. Pier Rosario Oliveira Joana Azeredo 《Applied microbiology》2005,71(12):8677-8682
Low concentrations of antibiotics can inhibit microbial adherence to medical device surfaces. However, little is known about the changes that occur in the physiology of bacteria within biofilms formed in the presence of subinhibitory (sub-MIC) concentrations of antibiotics. In this study, the densities and matrix compositions ofbiofilms formed by two coagulase-negative Staphylococcus species in the absence and in the presence of sub-MIC concentrations of dicloxacillin were evaluated. Biofilms formed in the presence of sub-MIC concentrations of dicloxacillin contained less biomass, and there were notable changes in the composition of the biofilm matrix. Changes in the spatial structure were also verified by confocal scanning laser microscopy, indicating that biofilms grown in the presence of sub-MIC concentrations of dicloxicilln had a lower cell density. Physiological alterations in the bacteria within biofilms grown in the presence of subinhibitory concentrations of the antibiotic were also evaluated. The results showed that there were differences in bacterial surface characteristics when cultures were grown in the presence of sub-MIC concentrations of dicloxacillin, including decreased hydrophobicity and decreased expression of the exopolysaccharide poly-N-acetylglucosamine. The elemental composition of the cell surface was also analyzed, and whereas in Staphylococcus epidermidis there were decreases in the oxygen and nitrogen contents, in Staphylococcus haemolyticus there were increases in these two parameters. Additionally, increases in resistance to several antibiotics were observed for the cells within biofilms formed in the presence of dicloxacillin. 相似文献
33.
Michele Tonelli Matteo Simone Bruno Tasso Federica Novelli Vito Boido Fabio Sparatore Giuseppe Paglietti Sabrina Pricl Gabriele Giliberti Sylvain Blois Cristina Ibba Giuseppina Sanna Roberta Loddo Paolo La Colla 《Bioorganic & medicinal chemistry》2010,18(8):2937-2953
Seventy-six 2-phenylbenzimidazole derivatives were synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against a panel of 10 RNA and DNA viruses. The most commonly affected viruses were, in decreasing order, CVB-2, BVDV, Sb-1, HSV-1, and YFV, while HIV-1 and VSV were not affected, and RSV, VV and Reo-1 were only susceptible to a few compounds. Thirty-nine compounds exhibited high activity (EC50 = 0.1–10 μM) against at least one virus, and four of them were outstanding for their high and selective activity against VV (24, EC50 = 0.1 μM) and BVDV (50, 51, and 53 with EC50 = 1.5, 0.8, and 1.0 μM, respectively). The last compounds inhibited at low micromolar concentrations the NS5B RdRp of BVDV and also of HCV, the latter sharing structural similarity with the former. The considered compounds represent attractive leads for the development of antiviral agents against poxviruses, pestiviruses and even HCV, which are important human and veterinary pathogens. 相似文献
34.
In the Baltic Sea area, the cladoceran Daphnia magna is commonly found in brackish water rockpools and it has been suggested that salinity is one of the niche dimensions that affects the distribution of the species. The salinity tolerance of D. magna was studied both in physiological and life history experiments. The experimental salinities were freshwater, 4S and 8S. The highest respiration and ammonium excretion rates were measured in the freshwater treatment with decreasing respiration and ammonium excretion rates at higher salinities. The lowest O/N ratio (oxygen consumption to ammonium excretion), describing the metabolic status of an organism, was obtained at 8S, although the only significant differences were detected when comparing to 4S treatments. Individual growth rate, reproductive output and population growth rate were highest at 4S. At 8S growth and reproduction were reduced as compared to freshwater and 4S. The life history parameters in the performed experiments indicated higher fitness (expressed as r) as well as more favourable conditions for growth and reproduction at 4S, whereas the O/N ratio was more difficult to interpret and, in this case, gave a less clear picture of the salinity influence. 相似文献
35.
Role of recycling endosomes and lysosomes in dynein-dependent entry of canine parvovirus 总被引:5,自引:5,他引:5 下载免费PDF全文
Suikkanen S Sääjärvi K Hirsimäki J Välilehto O Reunanen H Vihinen-Ranta M Vuento M 《Journal of virology》2002,76(9):4401-4411
Canine parvovirus (CPV) is a nonenveloped virus with a 5-kb single-stranded DNA genome. Lysosomotropic agents and low temperature are known to prevent CPV infection, indicating that the virus enters its host cells by endocytosis and requires an acidic intracellular compartment for penetration into the cytoplasm. After escape from the endocytotic vesicles, CPV is transported to the nucleus for replication. In the present study the intracellular entry pathway of the canine parvovirus in NLFK (Nordisk Laboratory feline kidney) cells was studied. After clustering in clathrin-coated pits and being taken up in coated vesicles, CPV colocalized with coendocytosed transferrin in endosomes resembling recycling endosomes. Later, CPV was found to enter, via late endosomes, a perinuclear vesicular compartment, where it colocalized with lysosomal markers. There was no indication of CPV entry into the trans-Golgi or the endoplasmic reticulum. Similar results were obtained both with full and with empty capsids. The data thus suggest that CPV or its DNA was released from the lysosomal compartment to the cytoplasm to be then transported to the nucleus. Electron microscopy analysis revealed endosomal vesicles containing CPV to be associated with microtubules. In the presence of nocodazole, a microtubule-disrupting drug, CPV entry was blocked and the virus was found in peripheral vesicles. Thus, some step(s) of the entry process were dependent on microtubules. Microinjection of antibodies to dynein caused CPV to remain in pericellular vesicles. This suggests an important role for the motor protein dynein in transporting vesicles containing CPV along the microtubule network. 相似文献
36.
37.
Mutations in the chemotactic response regulator, CheY, that confer resistance to the phosphatase activity of CheZ 总被引:4,自引:3,他引:4
M. Germana Sanna Ronald V. Swanson Robert B. Bourret Melvin I. Simon 《Molecular microbiology》1995,15(6):1069-1079
CheY, a small cytoplasmic response regulator, plays an essential role in the chemotaxis pathway. The concentration of phospho-CheY is thought to determine the swimming behaviour of the cell: high levels of phospho-CheY cause bacteria to rotate their flagella clockwise and tumble, whereas low levels of the phos-phorylated form of the protein allow counter-ciockwise rotation of the flagella and smooth swimming. The phosphorylation state of CheY in vivo is determined by the activity of the phosphoryl donor CheA, and by the antagonistic effect of dephosphorylation of phospho-CheY. The dephosphorylation rate is controlled by the intrinsic autohydrolytic activity of phospho-CheY and by the CheZ protein, which accelerates dephosphorylation. We have analysed the effect of CheZ on the dephosphorylation rates of several mutant CheY proteins. Two point mutations were identified which were 50-fold and 5-fold less sensitive to the activity of CheZ than was the wild-type protein. Nonetheless, the phosphorylation and autodephos-phorylation rates of these mutants, CheY23ND and CheY26KE, were observed to be identical to those of wild-type CheY in the absence of CheZ. These are the first examples of CheY mutations that reduce sensitivity to the phosphatase activity of CheZ without being altered in terms of their intrinsic phosphorylation and autodephospborylation rates, interestingly, the residues Asn-23 and Lys-26 are located on a face of CheY far from the phosphorylation site (Asp-57), distinct from the previously described site of inter-action with the histidine kinase CheA, and partially overlapping with a region implicated in interaction with the flagellar switch. 相似文献
38.
Pichia fermentans DiSAABA 726 is a biofilm-forming yeast that undergoes dimorphic transition. Under yeast-like morphology it controls brown rot caused by Monilia spp. on apple fruit, while under pseudohyphal form, it shows pathogenic behaviour itself on peach fruit. The present study investigates the nutritional factors that induce and separate yeast-like and pseudohyphal morphologies under laboratory conditions. We show that P. fermentans DiSAABA 726 produces mainly yeast-like cells on media containing millimolar concentrations of urea and diammonium phosphate, and forms pseudohyphae at micromolar concentrations of these two salts. With ammonium sulphate, yeast-like or pseudohyphal morphology depends on the N concentration and the pH of the culture media. Amino acids such as methionine, valine, and phenylalanine invariably induce pseudohyphal morphology irrespective of the N concentration and the pH of the culture media. Methionol, 1-butanol, isobutanol, and isopropanol induce pseudohyphal growth, while phenylethanol and isoamyl alcohol fail to induce the formation of filaments. Thus, the morphogenesis of P. fermentans DiSAABA 726 depends more on the nitrogen source than on the N concentration, and is regulated by the quorum-sensing molecules that are generally produced from amino-acid assimilation under nitrogen starvation. 相似文献
39.
Alexander A. Baykov Anssi M. Malinen Heidi H. Luoto Reijo Lahti 《Microbiology and molecular biology reviews》2013,77(2):267-276
SUMMARY
In its early history, life appeared to depend on pyrophosphate rather than ATP as the source of energy. Ancient membrane pyrophosphatases that couple pyrophosphate hydrolysis to active H+ transport across biological membranes (H+-pyrophosphatases) have long been known in prokaryotes, plants, and protists. Recent studies have identified two evolutionarily related and widespread prokaryotic relics that can pump Na+ (Na+-pyrophosphatase) or both Na+ and H+ (Na+,H+-pyrophosphatase). Both these transporters require Na+ for pyrophosphate hydrolysis and are further activated by K+. The determination of the three-dimensional structures of H+- and Na+-pyrophosphatases has been another recent breakthrough in the studies of these cation pumps. Structural and functional studies have highlighted the major determinants of the cation specificities of membrane pyrophosphatases and their potential use in constructing transgenic stress-resistant organisms. 相似文献40.
Mariagiuseppina Pellegrini Barbara Manconi Alessandra Olianas Maria Teresa Sanna Claudia Meloni Monica Pirastru Paolo Mereu Giovanni Leoni Bruno Masala Laura Manca 《Biochimica et Biophysica Acta (BBA)/General Subjects》2011