全文获取类型
收费全文 | 685篇 |
免费 | 33篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 8篇 |
2021年 | 22篇 |
2020年 | 8篇 |
2019年 | 17篇 |
2018年 | 25篇 |
2017年 | 17篇 |
2016年 | 27篇 |
2015年 | 42篇 |
2014年 | 47篇 |
2013年 | 50篇 |
2012年 | 61篇 |
2011年 | 48篇 |
2010年 | 35篇 |
2009年 | 29篇 |
2008年 | 44篇 |
2007年 | 49篇 |
2006年 | 39篇 |
2005年 | 29篇 |
2004年 | 23篇 |
2003年 | 28篇 |
2002年 | 21篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1982年 | 1篇 |
排序方式: 共有719条查询结果,搜索用时 15 毫秒
31.
Mente E Legeay A Houlihan DF Massabuau JC 《American journal of physiology. Regulatory, integrative and comparative physiology》2003,284(2):R500-R510
Many water-breathing animals have a strategy that consists of maintaining low blood PO2 values in a large range of water oxygenation level (4-40 kPa). This study examines the postprandial changes in O2 consumption, arterial blood PO2, and tissue protein synthesis in the shore crab Carcinus maenas in normoxic, O2-depleted, and O2-enriched waters to study the effects of this strategy on the O2 consumption and peptide bond formation after feeding. In normoxic water (21 kPa), the arterial PO2 was 1.1 kPa before feeding and 1.2 kPa 24 h later. In water with a PO2 of 3 kPa (arterial PO2 0.6 kPa), postprandial stimulation of protein synthesis and O2 consumption were blocked. The blockade was partial at a water PO2 of 4 kPa (arterial PO2 0.8 kPa). An increase in environmental PO2 (60 kPa, arterial PO2 10 kPa) resulted in an increase in protein synthesis compared with normoxic rates. It is concluded that the arterial PO2 spontaneously set in normoxic Carcinus limits the rates of protein synthesis. The rationale for such a strategy is discussed. 相似文献
32.
33.
Routsias JG Touloupi E Dotsika E Moulia A Tsikaris V Sakarellos C Sakarellos-Daitsiotis M Moutsopoulos HM Tzioufas AG 《Molecular medicine (Cambridge, Mass.)》2002,8(6):293-305
BACKGROUND: Autoantigen La/SSB is molecular target of humoral autoimmunity in patients with primary Sjogren's Syndrome (pSS) and systemic lupus erythematosus (SLE). In this study, we investigated the existence and possible influence of anti-idiotypic response to anti-La/SSB antibodies. MATERIALS AND METHODS: Synthetic peptide analogs (pep) of the major antigenic determinants of La/SSB (289-308 aa and 349-364 aa) were prepared. Based on "molecular recognition" theory, complementary peptides (cpep), derived by anti-parallel readings of the noncoding strand of La/SSB DNA encoding for its antigenic determinants, were constructed. Sera from 150 patients with anti-La/SSB antibodies, 30 patients without anti-La/SSB antibodies, and 42 normal individuals were tested against all four peptides. F(ab')(2) fragments from anti-peptide IgG were prepared and F(ab')(2) - IgG interactions were evaluated using a specific anti-idiotypic ELISA. RESULTS: All four peptides were recognized by anti-La positive sera (83% and 51% for pep and cpep 349-364 and 51% and 28% for pep and cpep289-308, respectively). Anti-cpep F(ab')(2 )bound to a common idiotype (Id) located within or spatially close to the antigen combining site of anti La/SSB (anti-pep) antibodies. Homologous and cross-inhibition experiments further confirmed this relation. The anti-idiotypic antibodies inhibited the anti-La/SSB antibody binding to recombinant La/SSB by 91%. To overcome the anti-idiotypic interference in anti-La/SSB detection, a specific assay was developed. Sera were heated for dissociation of Id-anti-Id complexes, anti-Id antibodies blocked with cpep, and anti-La/SSB reactivity was recovered. Application of this method to anti-Ro positive-anti-La/SSB "negative" sera showed that all anti-Ro/SSA positive autoimmune sera also possess anti-La/SSB antibodies. This reaction was not observed in 14 anti-Ro negative- anti-Sm/RNP positive sera from patients with SLE. CONCLUSIONS: Autoimmune sera from patients with pSS and SLE contain anti-idiotypic antibodies targeting a common anti-La/SSB idiotype. These antibodies can be detected using complementary peptides of La/SSB epitopes. The antiidiotypic antibodies mask the anti-La/SSB response. Hidden anti-La/SSB antibodies can be released and detected using complementary epitope analogs. 相似文献
34.
Dijols S Boucher JL Lepoivre M Lefevre-Groboillot D Moreau M Frapart Y Rekka E Meade AL Stuehr DJ Mansuy D 《Biochemistry》2002,41(30):9286-9292
A study of the oxidation of a series of guanidines related to L-arginine (L-Arg) and of various alkyl- and arylguanidines, by recombinant NO-synthase II (NOS II), led us to the discovery of the first non-alpha-amino acid guanidine substrate of NOS, acting as an efficient NO precursor. This compound, 3-(trifluoromethyl)propylguanidine, 4, led to a rate of NO formation (k(cat) = 220 +/- 50 min(-1)) only 2 times lower than that of L-Arg. Formation of 1 mol of NO upon NOS II-catalyzed oxidation of 4 occurred with consumption of 2.9 mol of NADPH, which corresponds to a 52% coupling between electron transfer and oxygenation of its guanidine function. Its oxidation by activated mouse macrophages in an L-Arg-free medium resulted in NO(2)(-) formation that was inhibited by classical NOS inhibitors with a rate only 2-3 times lower than that observed with L-Arg itself. These results open the way toward the research of selective, stable guanidine substrates of NOS that could be interesting, new NO donors after in situ oxidation by a given NOS isoform. 相似文献
35.
36.
Koukaki M Giannoutsou E Karagouni A Diallinas G 《Journal of microbiological methods》2003,55(3):687-695
We systematically investigated the efficiency of Aspergillus nidulans transformation using protoplasts prepared from different stages of conidiospore germination and young mycelium. Using standard integrative plasmids, increased transformation yields were obtained with protoplasts isolated from a specific stage coincident with germ tube emergence. This increase ranged, on the average, from two- to eightfold depending on different plasmids used. Transformation efficiencies with a replicative plasmid were similar to those obtained using previously described methods. Although this observation suggests that elevated transformation efficiencies might be due to increased efficiency of recombination between plasmid and genomic sequences, we cannot exclude other factors associated with the particular developmental stage used. In the course of this study, we also examined the effect of other parameters that might enhance transformation yields. The method described is also significantly easier and faster than other current methods. 相似文献
37.
Myrianthefs P Karatzas S Venetsanou K Grouzi E Evagelopoulou P Boutzouka E Fildissis G Spiliotopoulou I Baltopoulos G 《Cytokine》2003,24(6):286-292
We examined seasonal differences in whole blood cytokine production after endotoxin (LPS) stimulation in 17 healthy individuals from an urban area having normal sleep/wakefulness pattern. We used 500 pg/ml of LPS for incubation period of 4 h to stimulate 100 microl of whole blood of the same subjects in June, September, February, and March. We found no differences in the circulating total WBCs and differentials including monocytes between different seasons. We found during September (autumn) a reduced pro-inflammatory cytokine production in terms of TNF-alpha and IL-6 production compared to the other seasons. We also found a reduced anti-inflammatory cytokine production in June (summer) and September (autumn) in terms of IL-10, TNF-RI and TNF-RII compared to February (winter) and March (spring). Our results suggest that in early summer there is a predominating pro-inflammatory cytokine response which is counterbalanced early in autumn. These results may have significant implications in the determination of reference values, in exploration of immune response and inflammatory disease prevalence between different seasons, in determining LPS tolerance (immunoparalysis) and planning clinical trials and immunomodulary therapies. However, the effect of dark/light exposure differences on the circadian periodicity in the responsiveness of immune cells during different seasons should be further investigated. 相似文献
38.
Kremastinou J Tzanakaki G Levidiotou S Markou F Themeli E Voyiatzi A Psoma E Theodoridou M Blackwell CC 《FEMS immunology and medical microbiology》2003,39(1):23-29
In response to an increase in the number of cases of invasive meningococcal disease (IMD) in northern regions of Greece, a survey was carried out to determine if there was an increase in carriage of Neisseria meningitidis, particularly in areas where there have been increases in immigrant populations from neighbouring countries. The second objective was to determine if there was an increase in the serogroup C:2a:P1.5,2 a phenotype associated with recent outbreaks or changes in antibiotic sensitivities. As carriage of Neisseria lactamica is associated with development of natural immunity to IMD, the third objective was to determine the carriage rate of N. lactamica in this population. Among 3167 individuals tested, meningococci were isolated from 334 (10.5%). Compared with our previous studies, the proportion of meningococcal carriers was significantly increased among children in secondary education (11.3%) (chi2=9.67, P<0.005) and military recruits (37.4%) (chi2=21.11, P<0.000). Only 5/334 (1.5%) isolates expressed the phenotype associated with the increase in IMD in Greece. N. lactamica was isolated from 146/3167 (4.6%) participants. It was isolated from 71/987 (7.2%) children attending primary or nursery schools; however, the highest proportion of carriers (11.3%) was found in the boarding school for young Albanian men. In the 21-59-year age range, the majority of N. lactamica isolates (22/25, 88%) were from women, probably due to closer or more prolonged contact with children in the primary school age range. Smoking was significantly associated with isolation of meningococci from men but not from women. Penicillin-insensitive strains (25/334, 7.5%) were identified in all four regions examined; the majority (14/25, 56%) were obtained from military personnel. We conclude that there was a higher proportion of carriers in the population of northern Greece; however, the increase in carriage rate was not associated with the influx of immigrants from neighbouring countries, and there was not a higher incidence of the C:2a:P1.5,2 strain responsible for increased disease activity in Greece in either the immigrant or local populations. 相似文献
39.
Tzetis M Efthymiadou A Strofalis S Psychou P Dimakou A Pouliou E Doudounakis S Kanavakis E 《Human genetics》2001,108(3):216-221
In order to investigate the incidence of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and unclassified variants in chronic pulmonary disease in children and adults, we studied 20 patients with asthma, 19 with disseminated bronchiectasis (DB) of unknown aetiology, and 12 patients with chronic obstructive pulmonary disease (COPD), and compared the results to 52 subjects from the general Greek population. Analysis of the whole coding region of the CFTR gene and its flanking intronic regions revealed that the proportion of CFTR mutations was 45% in asthma (P<0.05), 26.3% in DB (P>0.05), 16.7% in COPD (P>0.05), compared to 15.4% in the general population. Seventeen different molecular defects involved in disease predisposition were identified in 16 patients. Three potentially disease-causing mutations, T388 M, M1R and V11I, are novel, found so far only in three asthma patients. The hyperactive M470 allele was found more frequently in COPD patients (frequency 70.8%, P<0.01) than in the controls. The study of the TGmTnM470 V polyvariant CFTR allele revealed the presence of CFTR function-modulating haplotypes TG13/T5/M470, TG11/T5/M470, TG12/T5/V470 and TG12/T7, combined with M470 or V470, in six asthma patients, four DB patients (P<0.01), and two COPD patients (P<0.05). These results confirm the involvement of the CFTR gene in asthma, DB and possibly in COPD. 相似文献
40.
The crystals of the soil-isolated Bacillus thuringiensis (Bt) strain A4 consist of two polypeptides with molecular mass of 140 kDa and 32 kDa that exhibit insecticidal activity against
adult flies of Bactrocera oleae (Diptera). Plasmid curing applied to this strain resulted in the isolation of several subclones exhibiting alterations in
their crystal polypeptides as well as two acrystalliferous subclones. The crystals of subclone 1.1 lacked the 32-kDa polypeptide
and consisted uniquely of a 140-kDa polypeptide antigenically related to the parental 140-kDa crystal polypeptide. Additionally,
the crystals of this subclone exhibited insecticidal activity against B. oleae equivalent to that of the parental strain. Therefore, the 32-kDa crystal polypeptide is dispensable for insecticidal activity,
which appears to be dependent on the presence of the 140-kDa crystal polypeptide.
Received: 5 April 2000 / Accepted 2 May 2000 相似文献