全文获取类型
收费全文 | 491篇 |
免费 | 48篇 |
出版年
2022年 | 5篇 |
2021年 | 11篇 |
2020年 | 7篇 |
2019年 | 3篇 |
2018年 | 10篇 |
2017年 | 11篇 |
2016年 | 13篇 |
2015年 | 30篇 |
2014年 | 34篇 |
2013年 | 39篇 |
2012年 | 52篇 |
2011年 | 44篇 |
2010年 | 20篇 |
2009年 | 23篇 |
2008年 | 32篇 |
2007年 | 36篇 |
2006年 | 33篇 |
2005年 | 18篇 |
2004年 | 17篇 |
2003年 | 17篇 |
2002年 | 17篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1973年 | 2篇 |
1970年 | 2篇 |
1967年 | 1篇 |
1966年 | 2篇 |
1958年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有539条查询结果,搜索用时 218 毫秒
131.
Patschan S Li H Brodsky S Sullivan D De Angelis DA Patschan D Goligorsky MS 《American journal of physiology. Heart and circulatory physiology》2006,290(6):H2210-H2219
Glycosylphosphatidylinositol (GPI)-anchored proteins have been shown to cluster in microdomains enriched in glycosphingolipids and cholesterol and represent a relatively selective marker of lipid rafts. In recent years, several attempts have been made to use fluorescent probes to nondisruptively label these domains in living cells. Here, we have transfected endothelial cells with a GPI-anchored thermotolerant green fluorescent protein (ttGFP) to show colocalization of this fluoroprobe with another marker of lipid rafts, urokinase-type plasminogen activator receptor-1. ttGFP was used to quantify the cell surface area occupied by lipid rafts and to examine the effect of various proatherogenic signals on lipid rafts. Exposure of endothelial cells to asymmetric dimethylarginine and oxidized LDL (oxLDL), as well as oxidant stress, reduced the cell surface area occupied by lipid rafts. Next, the property of ttGFP to undergo a shift in absorbance depending on the clustering of these molecules was utilized to perform proximity imaging (PRIM). PRIM showed that nitric oxide (NO) increased the distance between GPI-anchored ttGFP molecules clustered in lipid-rich microdomains. This "unclustering" of GPI-anchored ttGFP was not reproduced by prooxidant signals and was due to reduction in membrane-cytoskeletal constraints on the lipid rafts. These findings suggested that two fundamentally different mechanisms modulate lipid rafts: 1) substance regulation of lipid rafts involving modification of cholesterol and sphingolipids and 2) structural regulation of lipid rafts through disruption of membrane-cytoskeletal interactions, switching off the spatial confinement of lipid rafts. 相似文献
132.
Fagerberg D Angström J Halim A Hultberg A Rakhimova L Hammarström L Borén T Teneberg S 《Glycobiology》2009,19(2):182-191
The "Le(b) mouse" was established as a model for investigations of the molecular events following Le(b)-mediated adhesion of Helicobacter pylori to the gastric epithelium. By the expression of a human alpha-1,3/4-fucosyltransferase in the gastric pit cell lineage of FVB/N transgenic mice, a production of Le(b) glycoproteins in gastric pit and surface mucous cells was obtained in this "Le(b) mouse," as demonstrated by binding of monoclonal anti-Le(b) antibodies. To explore the effects of the human alpha-1,3/4-fucosyltransferase on glycosphingolipid structures, neutral glycosphingolipids were isolated from stomachs of transgenic alpha-1,3/4-fucosyltransferase-expressing mice. A glycosphingolipid recognized by BabA-expressing H. pylori was isolated and characterized by mass spectrometry and proton NMR as Fuc alpha 2Gal beta 3(Fuc alpha 4)GalNAc beta 4 Gal beta 4 Glc beta 1Cer, i.e., a novel Le(b)-like glycosphingolipid on a ganglio core. In addition, two other novel glycosphingolipids were isolated from the mouse stomach epithelium that were found to be nonbinding with regard to H. pylori. The first was a pentaglycosylceramide, GalNAc beta 3 Gal alpha 3(Fuc alpha 2)Gal beta 4 Glc beta 1Cer, in which the isoglobotetrasaccharide has been combined with Fuc alpha 2 to yield an isoglobotetraosylceramide with an internal blood group B determinant. The second one was an elongated fucosyl-gangliotetraosylceramide, GalNAc beta 3(Fuc alpha 2)Gal beta 3GalNAc beta 4Gal beta 4 Glc beta 1Cer. 相似文献
133.
Lena Jansson Jonas Ångström Michael Lebens Anne Imberty Annabelle Varrot Susann Teneberg 《Biochimie》2010
Enterotoxigenic Escherichia coli and Vibrio cholerae are well known causative agents of severe diarrheal diseases. Both pathogens produce AB5 toxins, with one enzymatically active A-subunit and a pentamer of receptor-binding B-subunits. The primary receptor for both B-subunits is the GM1 ganglioside (Galβ3GalNAcβ4(NeuAcα3)Galβ4GlcβCer), but the B-subunits from porcine isolates of E. coli also bind neolacto-(Galβ4GlcNAcβ-)terminated glycoconjugates and the B-subunits from human isolates of E. coli (hLTB) have affinity for blood group A type 2-(GalNAcα3(Fucα2)Galβ4GlcNAcβ-)terminated glycoconjugates. 相似文献
134.
Matthias May Sabine Brookman-May Bernd Hoschke Christian Gilfrich Friederike Kendel Susann Baxmann Stefan Wittke Stephan T. Kiessig Kurt Miller Manfred Johannsen 《Cancer immunology, immunotherapy : CII》2010,59(5):687-695
About 30% of renal cell carcinomas (RCC) will develop recurrence after surgery. Despite evidence for a significantly improved
survival by autologous tumour cell vaccination therapy, the procedure has not become standard. Between August 1993 and December
1996, 1,267 RCC patients undergoing radical nephrectomy in 84 German hospitals were subsequently treated by autologous tumour
cell vaccination therapy. The study group comprised 692 patients with complete follow-up (stages pT2-3, pNx-2, M0 based on
the TNM classification, 4th edition). Subsequent propensity-score matching according to 7 defined criteria with 861 control
patients undergoing nephrectomy alone without adjuvant treatment at the Carl-Thiem-Hospital Cottbus, resulted in 495 matched
pairs. Overall and stage-specific survival rates were analysed after a median follow-up of 131 months. The 5- and 10-year
overall survival (OS) rates were 80.6 and 68.9% in the vaccine group and 79.2 and 62.1% in the control group (p = 0.066). Patients with pT3 stage RCC revealed 5- and 10-year OS rates of 71.3 and 53.6% in the study group and 65.4 and
36.2% in the control group (p = 0.022). In multivariable analysis, patients in the vaccine group showed a significantly improved survival both in the whole
study group (HR = 1.28, p = 0.030) and in the subgroup presenting with pT3 stage tumours (HR = 1.67, p = 0.011). Adjuvant treatment with autologous vaccination therapy resulted in a significantly improved overall survival in
pT3 stage RCC patients, suggesting benefit especially in this subgroup. However, controlled clinical trials integrating the
recent TNM classification and further risk constellations are required to define additional patient groups that may derive
benefit from this treatment. 相似文献
135.
Mitogen-activated protein kinase (MAPK) signalling occurs in response to almost any change in the extracellular or intracellular milieu that affects the metabolism of the cell, organ or the entire organism. MAPK-dependent signal transduction is required for physiological metabolic adaptation, but inappropriate MAPK signalling contributes to the development of several interdependent pathological traits, collectively known as metabolic syndrome. Metabolic syndrome leads to life-threatening clinical consequences, such as type 2 diabetes. This Review provides an overview of the MAPK-signalling mechanisms that underly basic cellular metabolism, discussing their link to disease. 相似文献
136.
Stepan H Scheithauer S Dornhöfer N Krämer T Faber R 《Obesity (Silver Spring, Md.)》2006,14(5):770-773
Objectives: Obesity before and during pregnancy is associated with several obstetrics risk factors for both mother and fetus. The aim of this retrospective study was to analyze the influence of BMI before pregnancy on distinct perinatal parameters. Research Methods and Procedures: The study includes 5067 singleton pregnancies from 2001 to 2004 at the Department of Obstetrics and Gynecology, University of Leipzig. The study group was divided into BMI groups: <18.5, ≥18.5 to <25, ≥25 to <30, ≥30 to <35, ≥35 to <40, and ≥40 kg/m2. Analysis of perinatal data included rate of intrauterine death, rate of cesarean section and shoulder dystocia, time of hospital stay for mother and newborn, and gestational age of delivery. Neonatal outcome variables included percentage of newborns weighing >4000 grams, rate of umbilical cord pH <7.10, and rate of 1‐, 5‐, and 10‐minute Apgar scores of <8. Results: There was no difference in the gestational age at delivery among the groups. In the group with BMI ≥30 kg/m2, the cesarean section rate was significantly elevated to 25.1%, with a more dramatic increase up to 30.2% in the group with BMI ≥35 kg/m2 and 43.1% in the group with BMI ≥40 kg/m2, mainly because of a higher number of secondary cesarean sections. Although newborns of obese women showed worse initial neonatal adaptation, the 10‐minute Apgar values did not differ among the groups. The higher rate of operative deliveries and the trend to an increased rate of shoulder dystocia did not influence duration of the hospital stay for mothers and newborns or morbidity of both. Discussion: A high pre‐pregnancy BMI is clearly associated with a higher rate of cesarean section deliveries. However, under the compensating conditions of a tertiary perinatal center, overall morbidity of mothers and newborns seems not to be increased. 相似文献
137.
The imprint of the geographical, evolutionary and ecological context on species-area relationships 总被引:3,自引:0,他引:3
Species-area relationships (SAR) are fundamental in the understanding of biodiversity patterns and of critical importance for predicting species extinction risk worldwide. Despite the enormous attention given to SAR in the form of many individual analyses, little attempt has been made to synthesize these studies. We conducted a quantitative meta-analysis of 794 SAR, comprising a wide span of organisms, habitats and locations. We identified factors reflecting both pattern-based and dynamic approaches to SAR and tested whether these factors leave significant imprints on the slope and strength of SAR. Our analysis revealed that SAR are significantly affected by variables characterizing the sampling scheme, the spatial scale, and the types of organisms or habitats involved. We found that steeper SAR are generated at lower latitudes and by larger organisms. SAR varied significantly between nested and independent sampling schemes and between major ecosystem types, but not generally between the terrestrial and the aquatic realm. Both the fit and the slope of the SAR were scale-dependent. We conclude that factors dynamically regulating species richness at different spatial scales strongly affect the shape of SAR. We highlight important consequences of this systematic variation in SAR for ecological theory, conservation management and extinction risk predictions. 相似文献
138.
Reporting standards in experimental studies 总被引:1,自引:0,他引:1
139.
On the generality of the latitudinal diversity gradient 总被引:2,自引:0,他引:2
Hillebrand H 《The American naturalist》2004,163(2):192-211
The decline of biodiversity with latitude has received great attention, but both the concise pattern and the causes of the gradient are under strong debate. Most studies of the latitudinal gradient comprise only one or few organism types and are often restricted to certain region or habitat types. To test for significant variation in the gradient between organisms, habitats, or regions, a meta-analysis was conducted on nearly 600 latitudinal gradients assembled from the literature. Each gradient was characterized by two effect sizes, strength (correlation coefficient) and slope, and additionally by 14 variables describing organisms, habitats, and regions. The analysis corroborated the high generality of the latitudinal diversity decline. Gradients on regional scales were significantly stronger and steeper than on local scales, and slopes also varied with sampling grain. Both strength and slope increased with organism body mass, and strength increased with trophic level. The body mass-effect size relation varied for ecto- versus homeotherm organisms and for different dispersal types, suggesting allometric effects on energy use and dispersal ability as possible mechanisms for the body mass effect. Latitudinal gradients were weaker and less steep in freshwater than in marine or terrestrial environments and differed significantly between continents and habitat types. The gradient parameters were not affected by hemisphere or the latitudinal range covered. This analysis is the first to describe these general and significant patterns, which have important consequences for models aiming to explain the latitudinal gradient. 相似文献
140.
Endothelial Cell Swelling by Aldosterone 总被引:7,自引:0,他引:7
Oberleithner H Schneider SW Albermann L Hillebrand U Ludwig T Riethmüller C Shahin V Schäfer C Schillers H 《The Journal of membrane biology》2003,196(3):163-172
There is accumulating evidence that mineralocorticoids not only act on kidney but also on the cardiovascular system. We investigated the response of human umbilical venous endothelial cells (HUVECs) to aldosterone at a time scale of 20 minutes in absence and presence of the aldosterone antagonist spironolactone or other transport inhibitors. We applied atomic force microscopy (AFM), which measures cell volume and volume shifts between cytosol and cell nucleus. We observed an immediate cell volume increase (about 10%) approximately 1 min after addition of aldosterone (0.1 µmol/l), approaching a maximum (about 18%) 10 min after aldosterone treatment. Cell volume returned to normal 20 min after hormone exposure. Spironolactone (1 µmol/l) or amiloride (1 µmol/l) prevented the late aldosterone-induced volume changes but not the immediate change observed 1 min after hormone exposure. AFM revealed nuclear swelling 5 min after aldosterone addition, followed by nuclear shrinkage 15 min later. The Na+/H+ exchange blocker cariporide (10 µmol/l) was ineffective. We conclude: (i) Aldosterone induces immediate (1 min) swelling independently of plasma membrane Na+ channels and intracellular mineralocorticoid receptors followed by late mineralocorticoid receptor- and Na+-channel-dependent swelling. (ii) Intracellular macromolecule shifts cause the changes in cell volume. (iii) Both amiloride and spironolactone may be useful for medical applications to prevent aldosterone-induced vasculopathies. 相似文献