全文获取类型
收费全文 | 653篇 |
免费 | 37篇 |
出版年
2023年 | 4篇 |
2022年 | 7篇 |
2021年 | 16篇 |
2020年 | 12篇 |
2019年 | 13篇 |
2018年 | 14篇 |
2017年 | 13篇 |
2016年 | 18篇 |
2015年 | 50篇 |
2014年 | 40篇 |
2013年 | 45篇 |
2012年 | 64篇 |
2011年 | 61篇 |
2010年 | 32篇 |
2009年 | 35篇 |
2008年 | 34篇 |
2007年 | 35篇 |
2006年 | 35篇 |
2005年 | 30篇 |
2004年 | 24篇 |
2003年 | 30篇 |
2002年 | 18篇 |
2001年 | 7篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 6篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1976年 | 1篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有690条查询结果,搜索用时 46 毫秒
161.
Silvestro EM Nakano V Arana-Chavez VE Marques MV Avila-Campos MJ 《FEMS microbiology letters》2006,257(2):189-194
The effects of subinhibitory concentrations of clindamycin on the morphological, biochemical and genetic characteristics of species of the Bacteroides fragilis group isolated from children with diarrhea were determined. The minimal inhibitory and subinhibitory concentrations for clindamycin were determined. Minimal inhibitory concentration values ranging from 0.25 to 512 microg mL(-1) were observed. Cultures grown with clindamycin were used to determine the macroscopic morphological characteristics, cellular viability, ultrastructural characteristics and DNA integrity. Clindamycin did not alter colonial morphology, but after 6 h elongated cells were observed. Also, extracellular vesicles and electron-lucent areas inside the cytoplasm were observed. Bacteria treated with clindamycin also showed fragmentation of DNA as determined by electrophoresis. The alterations produced by clindamycin might be indicative of a possible modification of the structures involved in bacterial pathogenesis. 相似文献
162.
The platelet receptor for type III collagen (TIIICBP) is present in platelet membrane lipid microdomains (rafts) 总被引:2,自引:2,他引:0
Maurice P Waeckel L Pires V Sonnet P Lemesle M Arbeille B Vassy J Rochette J Legrand C Fauvel-Lafève F 《Histochemistry and cell biology》2006,125(4):407-417
Platelet interactions with collagen are orchestrated by the presence or the migration of platelet receptor(s) for collagen
into lipid rafts, which are specialized lipid microdomains from the platelet plasma membrane enriched in signalling proteins.
Electron microscopy shows that in resting platelets, TIIICBP, a receptor specific for type III collagen, is present on the
platelet membrane and associated with the open canalicular system, and redistributes to the platelet membrane upon platelet
activation. After platelet lysis by 1% Triton X-100 and the separation of lipid rafts on a discontinuous sucrose gradient,
TIIICBP is recovered in lipid raft-containing fractions and Triton X-100 insoluble fractions enriched in cytoskeleton proteins.
Platelet aggregation, induced by type III collagen, was inhibited after disruption of the lipid rafts by cholesterol depletion,
whereas platelet adhesion under static conditions did not require lipid raft integrity. These results indicate that TIIICBP,
a platelet receptor involved in platelet interaction with type III collagen, is localized within platelet lipid rafts where
it could interact with other platelet receptors for collagen (GP VI and α2β1 integrin) for efficient platelet activation.
Pascal Maurice and Ludovic Waeckel have contributed equally to this work. 相似文献
163.
Gabriela Ecco Javier Vernal Guilherme Razzera Carolina Tavares Viviane Isabel Serpa Santiago Arias Fabricio Klerynton Marchini Marco Aurlio Krieger Samuel Goldenberg Hernn Terenzi 《Gene》2009,448(1):1-6
Kynureninase has been described in bacteria, fungi and animals as an enzyme involved in the catabolic degradation pathway of l-tryptophan. This pyridoxal 5′-phosphate (PLP)-dependent enzyme catalyzes the hydrolytic cleavage of l-kynurenine and 3-hydroxy-l-kynurenine to yield l-alanine and either anthranilic or 3-hydroxyanthranilic acid, respectively. We identified a putative kynureninase gene from a Trypanosoma cruzi project aiming at the structural and functional characterization of more than 100 proteins differentially expressed during metacyclogenesis. This gene encodes a protein similar in size and sequence to kynureninases from other sources. This open reading frame was cloned and the recombinant enzyme was overexpressed. Recombinant T. cruzi kynureninase was purified to homogeneity and its identity was confirmed by mass spectrometry. The apparent molecular mass of the native T. cruzi kynureninase was estimated by gel filtration, suggesting that the protein is a homodimer. Circular dichroism spectrum indicated a mixture of α-helix and β-sheet structure, expected for an aminotransferase fold. l-kynurenine, preferentially hydrolyzed by prokaryotic inducible kynureninases, and 3-hydroxy-l-kynurenine, the preferred substrate in fungi and vertebrates, are both catabolized equally well by T. cruzi kynureninase. Further experimental assays will be performed to fully understand the importance of this enzyme for T. cruzi metabolism. 相似文献
164.
Gaseous conditions at natural CO2 springs (mofettes) affect many processes in these unique ecosystems. While the response of plants to extreme and fluctuating
CO2 concentrations ([CO2]) is relatively well documented, little is known on microbial life in mofette soil. Therefore, it was the aim of this study
to investigate the abundance and diversity of CO2-fixing bacteria in grassland soils in different distances to a natural carbon dioxide spring. Samples of the same soil type
were collected from the Stavešinci mofette, a natural CO2 spring which is known for very pure CO2 emissions, at different distances from the CO2 releasing vents, at locations that clearly differed in soil CO2 efflux (from 12.5 to over 200 μmol CO2 m−2 s−1 yearly average). Bulk and rhizospheric soil samples were included into analyses. The microbial response was followed by a
molecular analysis of cbbL genes, encoding for the large subunit of RubisCO, a carboxylase which is of crucial importance for C assimilation in chemolitoautotrophic
microbes. In all samples analyzed, the “red-like” type of cbbL genes could be detected. In contrast, the “green-like” type of cbbL could not be measured by the applied technique. Surprisingly, a reduction of “red-like” cbbL genes copies was observed in bulk soil and rhizosphere samples from the sites with the highest CO2 concentrations. Furthermore, the diversity pattern of “red-like” cbbL genes changed depending on the CO2 regime. This indicates that only a part of the autotrophic CO2-fixing microbes could adapt to the very high CO2 concentrations and adverse life conditions that are governed by mofette gaseous regime.
Urška Videmšek, Alexandra Hagn, Michael Schloter, and Dominik Vodnik contributed equally to this study. 相似文献
165.
Nilesh Patel Viviane Choy Philippe Malouf Jules Thibault 《Process Biochemistry》2009,44(10):1164-1171
A series of fed-batch experiments at different agitation speeds were performed using the industrially important strain Trichoderma reesei RUT C-30 in two different bioreactors to understand the close relationship that exists between the shear field within a bioreactor, the morphology of the microorganism, the rheology of cultivation broth, and the process performance. The two bioreactors, stirred tank bioreactor (STB) and reciprocating plate bioreactor (RPB), are characterized by a significantly different shear field to which microorganisms are exposed. Highest biomass concentration (ca. 15 g l−1) was obtained at higher agitation rates in both bioreactors due to better oxygen supply. However, better filter paper activities per mg of protein were obtained at lower agitation in both bioreactors. In both bioreactors, young and healthier fungi in the batch phase were not affected by shear even at higher agitation rates. However, during the fed-batch phase, higher degree of fragmentation of clump morphology at high agitation intensity was confirmed by image analysis. Also, the rheological analysis showed an increase in apparent viscosity during the batch phase and early fed-batch phase due to the increase in the biomass concentration. During the late stages of cultivation, the apparent viscosity decreased due to cell lysis and spore formation. 相似文献
166.
Falagan-Lotsch P Rodrigues MS Esteves V Vieira R Amendola LC Pagnoncelli D Paixão JC Gallo CV 《Genetics and molecular biology》2009,32(2):255-259
The X-ray repair cross-complementing Group1 (XRCC1) gene has been defined as essential in the base excision repair (BER) and single-strand break repair processes. This gene is highly polymorphic, and the most extensively studied genetic changes are in exon 6 (Arg194Trp) and in exon 10 (Arg399Gln). These changes, in conserved protein sites, may alter the base excision repair capacity, increasing the susceptibility to adverse health conditions, including cancer. In the present study, we estimated the frequencies of the XRCC1 gene polymorphisms Arg194Trp and Arg399Gln in healthy individuals and also in women at risk of breast cancer due to family history from Rio de Janeiro. The common genotypes in both positions (194 and 399) were the most frequent in this Brazilian sample. Although the 194Trp variant was overrepresented in women reporting familial cases of breast cancer, no statistically significant differences concerning genotype distribution or intragenic interactions were found between this group and the controls. Thus, in the population analyzed by us, variants Arg194Trp and Arg399Gln did not appear to have any impact on breast cancer susceptibility. 相似文献
167.
Matthew K. Nock Irving Hwang Nancy Sampson Ronald C. Kessler Matthias Angermeyer Annette Beautrais Guilherme Borges Evelyn Bromet Ronny Bruffaerts Giovanni de Girolamo Ron de Graaf Silvia Florescu Oye Gureje Josep Maria Haro Chiyi Hu Yueqin Huang Elie G. Karam Norito Kawakami Viviane Kovess Daphna Levinson Jose Posada-Villa Rajesh Sagar Toma Tomov Maria Carmen Viana David R. Williams 《PLoS medicine》2009,6(8)
Background
Suicide is a leading cause of death worldwide. Mental disorders are among the strongest predictors of suicide; however, little is known about which disorders are uniquely predictive of suicidal behavior, the extent to which disorders predict suicide attempts beyond their association with suicidal thoughts, and whether these associations are similar across developed and developing countries. This study was designed to test each of these questions with a focus on nonfatal suicide attempts.Methods and Findings
Data on the lifetime presence and age-of-onset of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) mental disorders and nonfatal suicidal behaviors were collected via structured face-to-face interviews with 108,664 respondents from 21 countries participating in the WHO World Mental Health Surveys. The results show that each lifetime disorder examined significantly predicts the subsequent first onset of suicide attempt (odds ratios [ORs] = 2.9–8.9). After controlling for comorbidity, these associations decreased substantially (ORs = 1.5–5.6) but remained significant in most cases. Overall, mental disorders were equally predictive in developed and developing countries, with a key difference being that the strongest predictors of suicide attempts in developed countries were mood disorders, whereas in developing countries impulse-control, substance use, and post-traumatic stress disorders were most predictive. Disaggregation of the associations between mental disorders and nonfatal suicide attempts showed that these associations are largely due to disorders predicting the onset of suicidal thoughts rather than predicting progression from thoughts to attempts. In the few instances where mental disorders predicted the transition from suicidal thoughts to attempts, the significant disorders are characterized by anxiety and poor impulse-control. The limitations of this study include the use of retrospective self-reports of lifetime occurrence and age-of-onset of mental disorders and suicidal behaviors, as well as the narrow focus on mental disorders as predictors of nonfatal suicidal behaviors, each of which must be addressed in future studies.Conclusions
This study found that a wide range of mental disorders increased the odds of experiencing suicide ideation. However, after controlling for psychiatric comorbidity, only disorders characterized by anxiety and poor impulse-control predict which people with suicide ideation act on such thoughts. These findings provide a more fine-grained understanding of the associations between mental disorders and subsequent suicidal behavior than previously available and indicate that mental disorders predict suicidal behaviors similarly in both developed and developing countries. Future research is needed to delineate the mechanisms through which people come to think about suicide and subsequently progress from ideation to attempts. Please see later in the article for Editors'' Summary 相似文献168.
169.
Viviane Aparecida Veronez Márcio Botelho de Castro Gervásio H. Bechara Matias P. J. Szabó 《Experimental & applied acarology》2010,50(2):151-161
Histological features of Rhipicephalus sanguineus ticks fed on dog, a non resistant host, and on guinea pig, a resistant host, were compared. Unfed ticks and ticks from each
host species were collected during first and third infestation and processed for histology. Many ticks from guinea pigs, especially
during third infestation, were unattached, dehydrated and small. Only the midgut of ticks fed on guinea pigs had host leukocytes.
Vacuolization of midgut cells was observed in all ticks, with exception of those fed on dogs for more than 96 h. Ticks of
guinea pigs, particularly from third infestation, had vacuolated tracheae and swelling of malpighian tubules. Solely ticks
from third infestation of guinea pigs displayed vacuolization of oocytes. Ticks fed on guinea pigs also had an increased number
of guanine spherules. Observed alterations in ticks from guinea pigs are discussed. 相似文献
170.
The Intra-Hippocampal Leucine Administration Impairs Memory Consolidation and LTP Generation in Rats
Viviane Glaser Valeria P. Carlini Laura Gabach Marisa Ghersi Susana Rubiales de Barioglio Oscar A. Ramirez Mariela F. Perez Alexandra Latini 《Cellular and molecular neurobiology》2010,30(7):1067-1075
Leucine accumulates in fluids and tissues of patients affected by maple syrup urine disease, an inherited metabolic disorder,
predominantly characterized by neurological dysfunction. Although, a variable degree of cognition/psychomotor delay/mental
retardation is found in a considerable number of individuals affected by this deficieny, the mechanisms underlying the neuropathology
of these alterations are still not defined. Therefore, the aim of this study was to investigate the effect of acute intra-hippocampal
leucine administration in the step-down test in rats. In addition, the leucine effects on the electrophysiological parameter,
long-term potentiation generation, and on the activities of the respiratory chain were also investigated. Male Wistar rats
were bilaterally administrated with leucine (80 nmol/hippocampus; 160 nmol/rat) or artificial cerebrospinal fluid (controls)
into the hippocampus immediately post-training in the behavioral task. Twenty-four hours after training in the step-down test,
the latency time was evaluated and afterwards animals were sacrificed for assessing the ex vivo biochemical measurements.
Leucine-treated animals showed impairment in memory consolidation and a complete inhibition of long-term potentiation generation
at supramaximal stimulation. In addition, a significant increment in complex IV activity was observed in hippocampus from
leucine-administered rats. These data strongly indicate that leucine compromise memory consolidation, and that impairment
of long-term potentiation generation and unbalance of the respiratory chain may be plausible mechanisms underlying the deleterious
leucine effect on cognition. 相似文献