全文获取类型
收费全文 | 551篇 |
免费 | 45篇 |
专业分类
596篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 14篇 |
2020年 | 4篇 |
2019年 | 2篇 |
2018年 | 8篇 |
2017年 | 3篇 |
2016年 | 9篇 |
2015年 | 15篇 |
2014年 | 25篇 |
2013年 | 42篇 |
2012年 | 54篇 |
2011年 | 54篇 |
2010年 | 29篇 |
2009年 | 30篇 |
2008年 | 33篇 |
2007年 | 37篇 |
2006年 | 38篇 |
2005年 | 24篇 |
2004年 | 39篇 |
2003年 | 22篇 |
2002年 | 16篇 |
2001年 | 2篇 |
2000年 | 9篇 |
1999年 | 9篇 |
1998年 | 14篇 |
1997年 | 11篇 |
1996年 | 1篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 9篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1986年 | 4篇 |
1985年 | 1篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1973年 | 2篇 |
1972年 | 3篇 |
1968年 | 1篇 |
排序方式: 共有596条查询结果,搜索用时 0 毫秒
31.
Chauzat MP Faucon JP Martel AC Lachaize J Cougoule N Aubert M 《Journal of economic entomology》2006,99(2):253-262
In 2002, a field survey was initiated on French apiaries to monitor weakness of honey bee, Apis mellifera L., colonies. Apiaries were evenly distributed in five sites located on continental France. Five colonies were randomly selected in each apiary, leading to a total of 125 studied honey bee colonies. For 3 yr (starting in autumn 2002), colonies were visited four times per year: after winter, before summer, during summer, and before winter. Pollen loads from traps were collected at each visit. Multiresidue analyses were performed in pollen to search residues of 36 different molecules. Specific analyses were conducted to search fipronil and metabolites and also imidacloprid and metabolites. Residues of 19 searched compounds were found in samples. Contamination by pesticides ranged from 50 to 0%. Coumaphos and tau-fluvalinate residues were the most concentrated of all residues (mean concentrations were 925.0 and 487.2 microg/kg, respectively). Fipronil and metabolite contents were superior to the limit of detection in 16 samples. Residues of fipronil were found in 10 samples. Nine samples contained the sulfone compound, and three samples contained the desulfinyl compound. Residues of imidacloprid and 6-chloronicotinic acid were found in 69% of samples. Imidacloprid contents were quantified in 11 samples with values ranging from 1.1 to 5.7 microg/kg. 6-Chloronicotinic acid content was superior to the limit of quantification in 28 samples with values ranging from 0.6 to 9.3 microg/kg. Statistical tests showed no difference between places of sampling with the exception of fipronil. Possible origins of these contaminations, concentration and toxicity of pesticides, and the possible consequences for bees are discussed. 相似文献
32.
Delphine Mariotte Beno?t Dupont Radj Gervais Marie-Pierre Galais Dominique Laroche Aurore Tranchant Elisabeth Comby Karine Bouhier-Leporrier Jean-Marie Reimund Brigitte Le Mauff 《MABS-AUSTIN》2011,3(4):396-401
Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, has proven effective in the treatment of metastatic colorectal cancer and squamous cell carcinoma of the head and neck. However, a high incidence of immediate hypersensitivity reactions (HSR) to cetuximab after the first infusion has been observed. We have developed a test for identification of patients likely to show treatment-related HSR to cetuximab. An enzyme-linked immunosorbent assay (ELISA) for detecting anti-cetuximab IgEs was developed and tested on serum samples collected from cancer patients before start of cetuximab treatment, and from healthy blood donors. Similar levels of anti-cetuximab IgE were detected in pre-treatment patient sera (24/92, 26.1%) and sera from healthy blood donors (33/117, 28.2%). HSR were observed in 14 out of the 92 patients (15.2%), and 8 of these (57.1%) were grade 3–4. Anti-cetuximab IgEs were detected in 7/8 of the patients (87.5%) with severe HSRs as compared with 14/78 patients (17.9%) with no HSR (p = 0.0002). Predictive value of the anti-cetuximab IgE test for HSR events of grades 3–4 was calculated using Receiver Operating Characteristics analysis. With a cut-off value of 29 arbitrary units for the anti-cetuximab IgE, the ELISA test showed a sensitivity of 87.5%, specificity of 82.1%, positive predictive value of 33.3% and negative predictive value of 98.5%. Anti-cetuximab IgE ELISA detection could be a valuable tool to help the physician anticipate an anaphylaxis episode following cetuximab infusion and opt for a suitable alternative treatment.Key words: anti-cetuximab antibodies, ELISA, hypersensitivity, therapeutic monoclonal antibody, ROC 相似文献
33.
Ryser-Degiorgis MP Jakubek EB af Segerstad CH Bröjer C Mörner T Jansson DS Lundén A Uggla A 《Journal of wildlife diseases》2006,42(1):182-187
To investigate the prevalence of Toxoplasma gondii infection in free-ranging Eurasian lynx (Lynx lynx) in Sweden, serosanguinous fluids and feces were collected from 207 carcasses of lynx killed or found dead from 1996 to 1998. Sera were tested for antibodies against T. gondii by the direct agglutination test, and 156 (75.4%) of the sera tested positive at antibody titers>or=40. Antibody prevalence was significantly lower in lynx originating from the northern parts of Sweden than in lynx from the more southern regions that are more densely populated by humans. Age-related differences also were found, with a significantly lower prevalence (55%) in juvenile (<1-yr-old) than in subadult and adult animals (82%). There was no significant difference in seroprevalence between males and females. Oocysts typical of T. gondii were not detected in any of the fecal samples. 相似文献
34.
Marie-Pierre Arvy 《Physiologia plantarum》1983,58(1):75-80
After incubation for 3 h with (75 Se) selenate, the selenium distribution in the bean plant (Phaseolus vulgaris L. cv. Contender) through a 29-day period showed an uneven distribution: roots and trifoliate leaves were richer in 75 Se than stem and primary leaves. The high selenium concentration of roots resulted from the retention of selenate by the root cells: at the end of the 29-day period about 60° of the radioactivity was always ethanol-soluble, and when analysed by paper chromatography, proved to be selenate. By contrast, much of the radioactivity of the leaves was ethanol-insoluble, 75 Se being quickly captured in metabolic processes which immobilize it. During plant development, a portion of the total selenium remains mobile and is continually mobilized to the younger organs which display a rapid growth rate. This delivery results from a progressive liberation of selenate retained by mature organs, especially the roots, and from turnover in older leaf tissues, especially the trifoliate leaves. 相似文献
35.
Janine Kimpel Stephen E. Braun Gang Qiu Fay Eng Wong Michelle Conolle J?rn E. Schmitz Christian Brendel Laurent M. Humeau Boro Dropulic John J. Rossi Annemarie Berger Dorothee von Laer R. Paul Johnson 《PloS one》2010,5(8)
Although a variety of genetic strategies have been developed to inhibit HIV replication, few direct comparisons of the efficacy of these inhibitors have been carried out. Moreover, most studies have not examined whether genetic inhibitors are able to induce a survival advantage that results in an expansion of genetically-modified cells following HIV infection. We evaluated the efficacy of three leading genetic strategies to inhibit HIV replication: 1) an HIV-1 tat/rev-specific small hairpin (sh) RNA; 2) an RNA antisense gene specific for the HIV-1 envelope; and 3) a viral entry inhibitor, maC46. In stably transduced cell lines selected such that >95% of cells expressed the genetic inhibitor, the RNA antisense envelope and viral entry inhibitor maC46 provided the strongest inhibition of HIV-1 replication. However, when mixed populations of transduced and untransduced cells were challenged with HIV-1, the maC46 fusion inhibitor resulted in highly efficient positive selection of transduced cells, an effect that was evident even in mixed populations containing as few as 1% maC46-expressing cells. The selective advantage of the maC46 fusion inhibitor was also observed in HIV-1-infected cultures of primary T lymphocytes as well as in HIV-1-infected humanized mice. These results demonstrate robust inhibition of HIV replication with the fusion inhibitor maC46 and the antisense Env inhibitor, and importantly, a survival advantage of cells expressing the maC46 fusion inhibitor both in vitro and in vivo. Evaluation of the ability of genetic inhibitors of HIV-1 replication to confer a survival advantage on genetically-modified cells provides unique information not provided by standard techniques that may be important in the in vivo efficacy of these genes. 相似文献
36.
Joël Chopineau Stéphane Robert Laurence Fenart Roméo Cecchelli Bernard Lagoutte Stéphanie Paitier Marie-Pierre Dehouck Dominique Domurado 《Letters in Peptide Science》1997,4(4-6):313-321
Acylated proteins play a crucial role in cellphysiology because of their increased interaction withmembranes. Their isolation is difficult as aconsequence of their low cellular concentration andtheir chemical preparation is problematic due tosolubility problems. Through the use of reversedmicelles, we produced tens of milligrams of acylatedribonucleases A, chosen as a model, purified them bysemi-preparative high performance liquidchromatography (HPLC) and characterized them by analyticalHPLC, capillary electrophoresis, mass spectrometry, peptide mapping, Edman degradation and enzyme activity. We nextscrutinized the interaction with an in vitro blood–brainbarrier model and demonstrated that palmitoylated andstearoylated ribonucleases A are transported from onecompartment to the other across the cellular monolayer,in contrast to the native enzyme. 相似文献
37.
Marie-Pierre Lézé Pascal Marchand Denis Loquet Manuela Kogler Guillaume Le Baut 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):549-557
The present study was designed to follow our pharmacomodulation work in the field of non-steroidal aromatase inhibitors. All target compounds 12a–h and 28a–h were tested in vitro for human placental aromatase inhibition, using testosterone or androstenedione as the substrate for the aromatase enzyme and the IC50 and relative potency to aminoglutethimide data are included. A SAR study indicated that 3-[(4-fluorophenyl)(1H-imidazol-1-yl)methyl]-1-ethyl-2-methyl-1H-indole (28?g) was a highly potent and selective aromatase inhibitor with IC50 value of 0.025?μM. 28?g was also a weak inhibitor of androstenedione synthesis. 相似文献
38.
Ingrid Bourgeois Emilie Camiade Raja Biswas Pascal Courtin Laure Gibert Friedrich Götz Marie-Pierre Chapot-Chartier Jean-Louis Pons & Martine Pestel-Caron 《FEMS microbiology letters》2009,290(1):105-113
The nucleotide sequence of atlL , a gene encoding a putative Staphylococcus lugdunensis peptidoglycan hydrolase, was determined using degenerate consensus PCR and genome walking. This 3837-bp gene encodes a protein, AtlL, that appears as a putative bifunctional autolysin with a 29-amino acid putative signal peptide and two enzymatic putative centres ( N -acetylmuramoyl- l -alanine amidase and N -acetylglucosaminidase) interconnected with three imperfect repeated sequences displaying glycine–tryptophan motifs. In order to determine whether both lytic domains were functional, and verify their exact enzymatic activities, gene fragments harbouring both putative domains, AM ( N -acetylmuramoyl- l -alanine amidase enzymatic centre plus two repeated sequences) and GL ( N -acetylglucosaminidase enzymatic centre plus one repeated sequence), were isolated, subcloned, and expressed in Escherichia coli . Purified recombinant AM and GL protein truncations exhibited cell wall lytic activity in zymograms performed with cell walls of Micrococcus lysodeikticus, Bacillus subtilis , and S. lugdunensis. AtlL is expressed during the whole growth, with an overexpression in the early-exponential stage. Liquid chromatography-mass spectrometry analysis of muropeptides generated by digestion of B. subtilis cell walls demonstrated the hydrolytic bond specificities and confirmed both of the acetyl domains' activities as predicted by sequence homology data. AtlL is the first autolysin described in S. lugdunensis , with a bifunctional enzymatic activity involved in peptidoglycan hydrolysis. 相似文献
39.
Mickaël Castelain Marie-Pierre Duviau Virginie Oxaran Philippe Schmitz Muriel Cocaign-Bousquet Pascal Loubière 《Biofouling》2016,32(8):911-923
The present work focuses on the role of pili present at the cell surface of Lactococcus lactis in bacterial adhesion to abiotic (hydrophobic polystyrene) and biotic (mucin-coated polystyrene) surfaces. Native pili-displaying strains and isogenic derivatives in which pilins or sortase C structural genes had been modified were used. Surface physico-chemistry, morphology and shear-flow-induced detachment of lactococcal cells were evaluated. The involvement of pili in L. lactis adhesion was clearly demonstrated, irrespective of the surface characteristics (hydrophobic/hydrophilic, presence or not of specific binding sites). The accessory pilin, PilC, and the backbone pilin, PilB, were revealed to play a major role in adhesion, provided that the PilB was present in its polymerized form. Within the population fraction that remained attached to the surface under increasing shear flow, different association behaviors were observed, showing that pili could serve as anchoring sites thus hampering the effect of shear flow on cell orientation and detachment. 相似文献
40.
Zhongli Gao William J. Hurst Etienne Guillot Raisa Nagorny Marie-Pierre Pruniaux James A. Hendrix Pascal G. George 《Bioorganic & medicinal chemistry letters》2013,23(14):4044-4047
This Letter describes the asymmetric synthesis of the four stereoisomers (8a–8d) of a potent and highly selective histamine H3 receptor (H3R) antagonist, 5-fluoro-2-methyl-N-[2-methyl-4-(2-methyl[1,3′]bipyrrolidinyl-1′-yl) phenyl]benzamide (1). The physico-chemical properties, in vitro H3R affinities and ADME of 8a–8d were determined. Stereoisomer 8c (2S,3′S) displayed superior in vitro H3R affinity over other three stereoisomers and was selected for further profiling in in vivo PK and drug safety. Compound 8c exhibited excellent PK properties with high exposure, desired brain to plasma ratio and reasonable brain half life. However, all stereoisomers showed similar unwanted hERG affinities. 相似文献