全文获取类型
收费全文 | 2051篇 |
免费 | 157篇 |
国内免费 | 1篇 |
出版年
2022年 | 8篇 |
2021年 | 39篇 |
2020年 | 18篇 |
2019年 | 27篇 |
2018年 | 47篇 |
2017年 | 27篇 |
2016年 | 60篇 |
2015年 | 103篇 |
2014年 | 95篇 |
2013年 | 120篇 |
2012年 | 209篇 |
2011年 | 144篇 |
2010年 | 109篇 |
2009年 | 112篇 |
2008年 | 142篇 |
2007年 | 127篇 |
2006年 | 106篇 |
2005年 | 107篇 |
2004年 | 105篇 |
2003年 | 106篇 |
2002年 | 91篇 |
2001年 | 17篇 |
2000年 | 14篇 |
1999年 | 18篇 |
1998年 | 24篇 |
1997年 | 17篇 |
1996年 | 12篇 |
1995年 | 10篇 |
1994年 | 16篇 |
1993年 | 11篇 |
1992年 | 13篇 |
1991年 | 11篇 |
1990年 | 14篇 |
1989年 | 6篇 |
1988年 | 9篇 |
1987年 | 13篇 |
1986年 | 4篇 |
1985年 | 9篇 |
1984年 | 8篇 |
1983年 | 5篇 |
1982年 | 8篇 |
1981年 | 8篇 |
1980年 | 6篇 |
1979年 | 6篇 |
1977年 | 4篇 |
1976年 | 6篇 |
1975年 | 6篇 |
1973年 | 4篇 |
1972年 | 5篇 |
1965年 | 3篇 |
排序方式: 共有2209条查询结果,搜索用时 31 毫秒
961.
Carole Rougé Marie-José Butel Hugues Piloquet Laurent Ferraris Arnaud Legrand Michel Vodovar Marcel Voyer Marie-France de la Cochetière Dominique Darmaun Jean-Christophe Rozé 《PloS one》2010,5(6)
Background
Fecal calprotectin has been proposed as a non-invasive marker of intestinal inflammation in inflammatory bowel disease in adults and children. Fecal calprotectin levels have been reported to be much higher in both healthy full-term and preterm infants than in children and adults.Objective
To determine the time course of fecal calprotectin (f-calprotectin) excretion in preterm infants from birth until hospital discharge and to identify factors influencing f-calprotectin levels in the first weeks of life, including bacterial establishment in the gut.Methodology
F-calprotectin was determined using an ELISA assay in 147 samples obtained prospectively from 47 preterm infants (gestational age, and birth-weight interquartiles 27–29 weeks, and 880–1320 g, respectively) at birth, and at 2-week intervals until hospital discharge.Principal Findings
Although median f-calprotectin excretion was 138 µg/g, a wide range of inter- and intra-individual variation in f-calprotectin values (from day 3 to day 78) was observed (86% and 67%, respectively). In multivariate regression analysis, f-calprotectin correlated negatively with ante and per natal antibiotic treatment (p = 0.001), and correlated positively with the volume of enteral feeding (mL/kg/d) (p = 0.009), the need to interrupt enteral feeding (p = 0.001), and prominent gastrointestinal colonization by Clostridium sp (p = 0.019) and Staphylococcus sp (p = 0.047).Conclusion
During the first weeks of life, the high f-calprotectin values observed in preterm infants could be linked to the gut bacterial establishment. 相似文献962.
Carole Nagant Marie Tré-Hardy Malika El-Ouaaliti Paul Savage Michel Devleeschouwer Jean-Paul Dehaye 《Applied microbiology and biotechnology》2010,88(1):251-263
The bactericidal activity of a cholic acid antimicrobial derivative, CSA-13, was tested against eight strains of Pseudomonas aeruginosa (both reference and clinical strains) and compared with the response to tobramycin. In planktonic cultures, the minimal inhibitory
and minimal bactericidal concentrations of CSA-13 and tobramycin were in the 1–25 mg/L range except for one mucoid clinical
strain which was much less sensitive to tobramycin (minimal bactericidal concentration, 65–125 mg/L). In young (24 h) biofilms,
the sensitivity to CSA-13 was reduced (half-maximal concentration CSA-13 averaged 88 mg/L) and varied among the eight strains.
The sensitivity to tobramycin was also very variable among the strains and some were fully resistant to the aminoglycoside.
The combination of tobramycin with CSA-13 was synergistic in five strains. Only one strain showed antagonism between the two
drugs at low concentrations of CSA-13. One reference and five clinical strains were tested in mature (12 days) biofilms. The
effect of CSA-13 was delayed, some strains requiring 9 days exposure to the drug to observe a bactericidal effect. All the
strains were tolerant to tobramycin but the addition of CSA-13 with tobramycin was synergistic in three strains. CSA-13 permeabilized
the outer membrane of the bacteria (half-maximal concentration, 4.4 mg/L). At concentrations higher than 20 mg/L, it also
permeabilized the plasma membrane of human umbilical vein endothelial cells. In conclusion, CSA-13 has bactericidal activity
against P. aeruginosa even in mature biofilms and cationic steroid antibiotics can thus be considered as potential candidates for the treatment
of chronic pulmonary infections of patients with cystic fibrosis. Considering its interaction with the plasma membrane of
eukaryotic cells, less toxic derivatives of CSA-13 should be developed. 相似文献
963.
964.
Morris A Swertz van der K Joeri Velde Bruno M Tesson Richard A Scheltema Danny Arends Gonzalo Vera Rudi Alberts Martijn Dijkstra Paul Schofield Klaus Schughart John M Hancock Damian Smedley Katy Wolstencroft Carole Goble Engbert O de Brock Andrew R Jones Helen E Parkinson Ritsert C Jansen 《Genome biology》2010,11(3):1-15
965.
966.
967.
Nitai C. Hait Carole A. Oskeritzian Steven W. Paugh Sarah Spiegel 《生物化学与生物物理学报:生物膜》2006,1758(12):2016-2026
Sphingolipids are ubiquitous components of cell membranes and their metabolites ceramide (Cer), sphingosine (Sph), and sphingosine-1-phosphate (S1P) have important physiological functions, including regulation of cell growth and survival. Cer and Sph are associated with growth arrest and apoptosis. Many stress stimuli increase levels of Cer and Sph, whereas suppression of apoptosis is associated with increased intracellular levels of S1P. In addition, extracellular/secreted S1P regulates cellular processes by binding to five specific G protein coupled-receptors (GPCRs). S1P is generated by phosphorylation of Sph catalyzed by two isoforms of sphingosine kinases (SphK), type 1 and type 2, which are critical regulators of the “sphingolipid rheostat”, producing pro-survival S1P and decreasing levels of pro-apoptotic Sph. Since sphingolipid metabolism is often dysregulated in many diseases, targeting SphKs is potentially clinically relevant. Here we review the growing recent literature on the regulation and the roles of SphKs and S1P in apoptosis and diseases. 相似文献
968.
969.
Synaptotagmins (syt) form a large family of transmembrane proteins and some of its isoforms are known to regulate calcium-induced membrane fusion during vesicular traffic. In view of the reported implication of the isoform syt8 in exocytosis we investigated the expression, localisation and calcium-sensitivity of syt8 in secretory cells. An immunopurified antipeptide antibody was generated which is directed against a C-terminal sequence and devoid of crossreactivity towards syt1 to 12. Subcellular fractionation and immunocytochemistry revealed two forms of synaptotagmin 8 (50 and 40 kDa). Whereas the 40-kDa was present in the cytosol in brain, in PC12 and in clonal beta-cells, the 50-kDa form was localised in very typical clusters and partially colocalised with the SNARE protein Vti1a. Moreover, in primary hippocampal neurons syt8 was only found within the soma. Amplification of syt8 by RT-PCR indicated that the observed protein variants were not generated by alternative splicing of the 6th exon and are most likely linked to variations in the N-terminal region. In contrast to the established calcium sensor syt2, endogenous cytosolic syt8 and transiently expressed syt8-C2AB-eGFP did not translocate upon a raise in cytosolic calcium in living cells. Syt8 is therefore not a calcium sensor in exocytotic membrane fusion in endocrine cells. 相似文献
970.
Effects of GPD1 overexpression in Saccharomyces cerevisiae commercial wine yeast strains lacking ALD6 genes 总被引:1,自引:0,他引:1
Cambon B Monteil V Remize F Camarasa C Dequin S 《Applied and environmental microbiology》2006,72(7):4688-4694
The utilization of Saccharomyces cerevisiae strains overproducing glycerol and with a reduced ethanol yield is a potentially valuable strategy for producing wine with decreased ethanol content. However, glycerol overproduction is accompanied by acetate accumulation. In this study, we evaluated the effects of the overexpression of GPD1, coding for glycerol-3-phosphate dehydrogenase, in three commercial wine yeast strains in which the two copies of ALD6 encoding the NADP+-dependent Mg2+-activated cytosolic acetaldehyde dehydrogenase have been deleted. Under wine fermentation conditions, the engineered industrial strains exhibit fermentation performance and growth properties similar to those of the wild type. Acetate was produced at concentrations similar to that of the wild-type strains, whereas sugar was efficiently diverted to glycerol. The ethanol yield of the GPD1 ald6 industrial strains was 15 to 20% lower than that in the controls. However, these strains accumulated acetoin at considerable levels due to inefficient reduction to 2,3-butanediol. Due to the low taste and odor thresholds of acetoin and its negative sensorial impact on wine, novel engineering strategies will be required for a proper adjustment of the metabolites at the acetaldehyde branch point. 相似文献