全文获取类型
收费全文 | 1922篇 |
免费 | 102篇 |
国内免费 | 2篇 |
出版年
2022年 | 4篇 |
2021年 | 16篇 |
2020年 | 3篇 |
2018年 | 7篇 |
2017年 | 9篇 |
2016年 | 18篇 |
2015年 | 32篇 |
2014年 | 56篇 |
2013年 | 80篇 |
2012年 | 80篇 |
2011年 | 78篇 |
2010年 | 73篇 |
2009年 | 68篇 |
2008年 | 123篇 |
2007年 | 117篇 |
2006年 | 120篇 |
2005年 | 117篇 |
2004年 | 119篇 |
2003年 | 101篇 |
2002年 | 126篇 |
2001年 | 23篇 |
2000年 | 13篇 |
1999年 | 32篇 |
1998年 | 39篇 |
1997年 | 30篇 |
1996年 | 35篇 |
1995年 | 26篇 |
1994年 | 29篇 |
1993年 | 31篇 |
1992年 | 32篇 |
1991年 | 19篇 |
1990年 | 26篇 |
1989年 | 26篇 |
1988年 | 20篇 |
1987年 | 16篇 |
1986年 | 17篇 |
1985年 | 24篇 |
1984年 | 26篇 |
1983年 | 18篇 |
1982年 | 35篇 |
1981年 | 24篇 |
1980年 | 29篇 |
1979年 | 17篇 |
1978年 | 14篇 |
1977年 | 16篇 |
1976年 | 12篇 |
1975年 | 9篇 |
1974年 | 15篇 |
1973年 | 9篇 |
1972年 | 6篇 |
排序方式: 共有2026条查询结果,搜索用时 31 毫秒
151.
Alain Bernadac Marthe Gavioli Jean-Claude Lazzaroni Satish Raina Roland Lloubs 《Journal of bacteriology》1998,180(18):4872-4878
Mutations in the tol-pal genes induce pleiotropic effects such as release of periplasmic proteins into the extracellular medium and hypersensitivity to drugs and detergents. Other outer membrane defective strains such as tolC, lpp, and rfa mutations are also altered in their outer membrane permeability. In this study, electron microscopy and Western blot analyses were used to show that strains with mutations in each of the tol-pal genes formed outer membrane vesicles after growth in standard liquid or solid media. This phenotype was not observed in tolC and rfaD cells in the same conditions. A tolA deletion in three different Escherichia coli strains was shown to lead to elevated amounts of vesicles. These results, together with plasmid complementation experiments, indicated that the formation of vesicles resulted from the defect of any of the Tol-Pal proteins. The vesicles contained outer membrane trimeric porins correctly exposed at the cell surface. Pal outer membrane lipoprotein was also immunodetected in the vesicle fraction of tol strains. The results are discussed in view of the role of the Tol-Pal transenvelope proteins in maintaining outer membrane integrity by contributing to target or integrate newly synthesized components of this structure. 相似文献
152.
Agarocolloids were extracted from field samples of Gracilaria gracilis, Gracilariopsis longissima and the newly reported Gracilaria
cf. vermiculophylla harvested at different periods of the year near Roscoff (France). Native and alkali modified extracts
were characterized by GLC, HPLC and FT-IR spectroscopy. The main components of agarocolloids isolated by freeze-thawing method,
were 3,6-anhydrogalactose and galactose. In addition, minor components (6-O-methyl-galactose, 4-O-methyl-galactose and sulfate
groups ranging from 4.4 up to 6.6% [w/w]) were detected. The highest rate of 6-O-methylgalactose was observed in agarocolloids
from vermiculophylla (14 mole%). Sulfates were mainly branched on C4 of the D-galactose in gracilis and Gs. longissima agarocolloids.
G. vermiculophylla agaroids isolated by EtOH and NaCl precipitations from the syneresis water were characterized by a high
sulfation on C6 of galactose and a low sulfation on C2 of 3,6-anhydrogalactose. Native agarocolloid gel strengths from Gracilaria
species were clearly higher than those of Gracilariopsis. Alkali treatments reduced the sulfate levels but increased slightly
the gel strengths. An approximation of the polymer sizes carried out with colorimetric assays indicated that the polymer sizes
were higher in G. gracilis than observed in Gs. longissima.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
153.
154.
Omar Riah Philippe Courrière Jean-Claude Dousset Nathalie Todeschi Christian Labat 《Cellular and molecular neurobiology》1998,18(3):311-318
1. Nicotine and its main metabolite, cotinine, were reported to have distinct behavioral activities in mammals.2. In this study, cotinine was synthesized without detectable nicotine contamination to compare the ability of nicotine and cotinine to pass the blood–brain barrier (BBB)in rats.3. The alkaloids were extracted from plasma and brain tissues by methanol, identified by thin-layer chromatography, and quantified by high-pressure liquid chromatography and radioimmunoassays.4. Consistently, the three methods showed that the passage of cotinine was time, route of administration, and dose dependent and that nicotine was more efficient than cotinine to pass the BBB.5. The results suggest that these alkaloids may have central activities that probably result from their actions at distinct molecular levels. 相似文献
155.
Jean-Claude Chalchat Raymond-Philippe Garry André Michet Alain Remery 《Phytochemistry》1985,24(10):2443-2444
The essential oils of Pinus sylvestris from French Massif Central are described. Forty-six compounds have been identified by spectral methods. Two chemotypes are recognized. 相似文献
156.
Hussein Akil Amazigh Abbaci Fabrice Lalloué Barbara Bessette Léa M. M. Costes Linda Domballe Sandrine Charreau Karline Guilloteau Lucie Karayan-Tapon Fran?ois-Xavier Bernard Franck Morel Marie-Odile Jauberteau Jean-Claude Lecron 《PloS one》2015,10(3)
Interleukin-22 (IL-22) is a member of the IL-10 cytokine family that binds to a heterodimeric receptor consisting of IL-22 receptor 1 (IL-22R1) and IL-10R2. IL-22R expression was initially characterized on epithelial cells, and plays an essential role in a number of inflammatory diseases. Recently, a functional receptor was detected on cancer cells such as hepatocarcinoma and lung carcinoma, but its presence was not reported in glioblastoma (GBM). Two GBM cell lines and 10 primary cell lines established from patients undergoing surgery for malignant GBM were used to investigate the expression of IL-22 and IL-22R by using quantitative RT-PCR, western blotting and confocal microscopy studies. The role of IL-22 in proliferation and survival of GBM cell lines was investigated in vitro by BrdU and ELISA cell death assays. We report herein that the two subunits of the IL-22R complex are expressed on human GBM cells. Their activation, depending on exogenous IL-22, induced antiapoptotic effect and cell proliferation. IL-22 treatment of GBM cells resulted in increased levels of phosphorylated Akt, STAT3 signaling protein and its downstream antiapoptotic protein Bcl-xL and decreased level of phosphorylated ERK1/2. In addition, IL-22R subunits were expressed in all the 10 tested primary cell lines established from GBM tumors. Our results showed that IL-22R is expressed on GBM established and primary cell lines. Depending on STAT3, ERK1/2 and PI3K/Akt pathways, IL-22 induced GBM cell survival. These data are consistent with a potential role of IL-22R in tumorigenesis of GBM. Since endogenous IL-22 was not detected in all studied GBM cells, we hypothesize that IL-22R could be activated by immune microenvironmental IL-22 producing cells. 相似文献
157.
Alexandra Mangili Julian Falutz Jean-Claude Mamputu Miganush Stepanians Brooke Hayward 《PloS one》2015,10(10)
BackgroundTesamorelin, a synthetic analog of human growth hormone-releasing factor, decreases visceral adipose tissue (VAT) in human immunodeficiency virus (HIV)-infected patients with lipodystrophy.Objectives1) To evaluate the utility of patient characteristics and validated disease-risk scores, namely indicator variables for the metabolic syndrome defined by the International Diabetes Federation (MetS-IDF) or the National Cholesterol Education Program (MetS-NCEP) and the Framingham Risk Score (FRS), as predictors of VAT reduction during tesamorelin therapy at 3 and 6 months, and 2) To explore the characteristics of patients who reached a threshold of VAT <140 cm2, a level associated with lower risk of adverse health outcomes, after 6 months of treatment with tesamorelin.MethodsData were analyzed from two Phase 3 studies in which HIV-infected patients with excess abdominal fat were randomized in a 2:1 ratio to receive tesamorelin 2 mg (n = 543) or placebo (n = 263) subcutaneously daily for 6 months, using ANOVA and ANCOVA models.ResultsMetabolic syndrome (MetS-IDF or MetS-NCEP) and FRS were significantly associated with VAT at baseline. Presence of metabolic syndrome ([MetS-NCEP), triglyceride levels >1.7 mmol/L, and white race had a significant impact on likelihood of response to tesamorelin after 6 months of therapy (interaction p-values 0.054, 0.063, and 0.025, respectively). No predictive factors were identified at 3 months. The odds of a VAT reduction to <140 cm2 for subjects treated with tesamorelin was 3.9 times greater than that of subjects randomized to placebo after controlling for study, gender, baseline body mass index (BMI) and baseline VAT (95% confidence interval [CI] 2.03; 7.44).ConclusionsIndividuals with baseline MetS-NCEP, elevated triglyceride levels, or white race were most likely to experience reductions in VAT after 6 months of tesamorelin treatment. The odds of response of VAT <140 cm2 was 3.9 times greater for tesamorelin-treated patients than that of patients receiving placebo. 相似文献
158.
Blanda Di Luccia Raffaella Crescenzo Arianna Mazzoli Luisa Cigliano Paola Venditti Jean-Claude Walser Alex Widmer Loredana Baccigalupi Ezio Ricca Susanna Iossa 《PloS one》2015,10(8)
A fructose-rich diet can induce metabolic syndrome, a combination of health disorders that increases the risk of diabetes and cardiovascular diseases. Diet is also known to alter the microbial composition of the gut, although it is not clear whether such alteration contributes to the development of metabolic syndrome. The aim of this work was to assess the possible link between the gut microbiota and the development of diet-induced metabolic syndrome in a rat model of obesity. Rats were fed either a standard or high-fructose diet. Groups of fructose-fed rats were treated with either antibiotics or faecal samples from control rats by oral gavage. Body composition, plasma metabolic parameters and markers of tissue oxidative stress were measured in all groups. A 16S DNA-sequencing approach was used to evaluate the bacterial composition of the gut of animals under different diets. The fructose-rich diet induced markers of metabolic syndrome, inflammation and oxidative stress, that were all significantly reduced when the animals were treated with antibiotic or faecal samples. The number of members of two bacterial genera, Coprococcus and Ruminococcus, was increased by the fructose-rich diet and reduced by both antibiotic and faecal treatments, pointing to a correlation between their abundance and the development of the metabolic syndrome. Our data indicate that in rats fed a fructose-rich diet the development of metabolic syndrome is directly correlated with variations of the gut content of specific bacterial taxa. 相似文献
159.
Isabelle Perrault Fadi?F. Hamdan Marlène Rio José-Mario Capo-Chichi Nathalie Boddaert Jean-Claude Décarie Bruno Maranda Rima Nabbout Michel Sylvain Anne Lortie Philippe?P. Roux Elsa Rossignol Xavier Gérard Giulia Barcia Patrick Berquin Arnold Munnich Guy?A. Rouleau Josseline Kaplan Jean-Michel Rozet Jacques?L. Michaud 《American journal of human genetics》2014,94(6):891-897
Epileptic encephalopathies are increasingly thought to be of genetic origin, although the exact etiology remains uncertain in many cases. We describe here three girls from two nonconsanguineous families affected by a clinical entity characterized by dysmorphic features, early-onset intractable epilepsy, intellectual disability, and cortical blindness. In individuals from each family, brain imaging also showed specific changes, including an abnormally marked pontobulbar sulcus and abnormal signals (T2 hyperintensities) and atrophy in the occipital lobe. Exome sequencing performed in the first family did not reveal any gene with rare homozygous variants shared by both affected siblings. It did, however, show one gene, DOCK7, with two rare heterozygous variants (c.2510delA [p.Asp837Alafs∗48] and c.3709C>T [p.Arg1237∗]) found in both affected sisters. Exome sequencing performed in the proband of the second family also showed the presence of two rare heterozygous variants (c.983C>G [p.Ser328∗] and c.6232G>T [p.Glu2078∗]) in DOCK7. Sanger sequencing confirmed that all three individuals are compound heterozygotes for these truncating mutations in DOCK7. These mutations have not been observed in public SNP databases and are predicted to abolish domains critical for DOCK7 function. DOCK7 codes for a Rac guanine nucleotide exchange factor that has been implicated in the genesis and polarization of newborn pyramidal neurons and in the morphological differentiation of GABAergic interneurons in the developing cortex. All together, these observations suggest that loss of DOCK7 function causes a syndromic form of epileptic encephalopathy by affecting multiple neuronal processes. 相似文献
160.
Zonula Occludens (ZO) proteins are ubiquitous scaffolding proteins providing the structural basis for the assembly of multiprotein complexes at the cytoplasmic surface of the plasma membrane and linking transmembrane proteins to the filamentous cytoskeleton. They belong to the large family of membrane-associated guanylate kinase (MAGUK)-like proteins comprising a number of subfamilies based on domain content and sequence similarity. ZO proteins were originally described to localize specifically to tight junctions, or Zonulae Occludentes, but this notion was rapidly reconsidered since ZO proteins were found to associate with adherens junctions as well as with gap junctions, particularly with connexin-made intercellular channels, and also with a few other membrane channels. Accumulating evidence reveals that in addition to having passive scaffolding functions in organizing gap junction complexes, including connexins and cytoskeletals, ZO proteins (particularly ZO-1) also actively take part in the dynamic function as well as in the remodeling of junctional complexes in a number of cellular systems. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé. 相似文献