全文获取类型
收费全文 | 2776篇 |
免费 | 267篇 |
专业分类
3043篇 |
出版年
2022年 | 23篇 |
2021年 | 43篇 |
2020年 | 19篇 |
2019年 | 18篇 |
2018年 | 34篇 |
2017年 | 31篇 |
2016年 | 45篇 |
2015年 | 92篇 |
2014年 | 110篇 |
2013年 | 127篇 |
2012年 | 182篇 |
2011年 | 173篇 |
2010年 | 112篇 |
2009年 | 89篇 |
2008年 | 165篇 |
2007年 | 135篇 |
2006年 | 140篇 |
2005年 | 125篇 |
2004年 | 114篇 |
2003年 | 124篇 |
2002年 | 116篇 |
2001年 | 31篇 |
2000年 | 19篇 |
1999年 | 26篇 |
1998年 | 23篇 |
1997年 | 34篇 |
1996年 | 21篇 |
1994年 | 19篇 |
1993年 | 34篇 |
1992年 | 20篇 |
1991年 | 25篇 |
1990年 | 28篇 |
1987年 | 16篇 |
1986年 | 18篇 |
1985年 | 27篇 |
1984年 | 34篇 |
1983年 | 25篇 |
1982年 | 36篇 |
1981年 | 28篇 |
1980年 | 37篇 |
1979年 | 18篇 |
1978年 | 27篇 |
1977年 | 30篇 |
1976年 | 26篇 |
1974年 | 17篇 |
1973年 | 25篇 |
1972年 | 22篇 |
1971年 | 18篇 |
1970年 | 17篇 |
1969年 | 18篇 |
排序方式: 共有3043条查询结果,搜索用时 15 毫秒
41.
Edwin T. H. M. Peeters Bart T. M. J. Brugmans John A. J. Beijer Rob J. M. Franken 《Aquatic Ecology》2006,40(3):373-380
The herbivorous mayfly Heptagenia sulphurea is characteristic of rivers with stony bottoms. Records from the 20th century showed that this species had disappeared from the Common Meuse in the Netherlands, probably due to river regulation or changes in water quality. A field survey in 2003 showed that H. sulphurea was present in the Geul tributary, approximately 300 m upstream of its confluence with the Common Meuse. H. sulphurea has not recolonized the Common Meuse despite improvements in water quality over the last decades. Concentration of suspended sediments in the River Meuse, however, is still high, much higher than in the beginning of the 20th century. The presence of a silt layer may limit the return of H. sulphurea in this river by reducing availability and quality of its food. The prime objective of this study was to investigate the impact of silt on survival and growth of H. sulphurea in a laboratory experiment. Furthermore, the impact of water and periphyton quality from the Common Meuse on survival and growth of this mayfly was also investigated. Results showed that neither water quality nor cultured periphyton from the Common Meuse reduced survival and growth of H. sulphurea. The presence of a silt layer resulted in a significantly lower growth rate of the mayfly larvae. It is concluded that the silt layer reduces the accessibility of the food. Covering of food is possibly one of the main factors limiting the recolonization of H. sulphurea and probably other benthic grazers in the Common Meuse. 相似文献
42.
Jennifer A Dickens Bruce E Miller Lisa D Edwards Edwin K Silverman David A Lomas Ruth Tal-Singer 《Respiratory research》2011,12(1):146
Background
There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions. A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) cohort.Methods
Thirty-four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort. Biomarker repeatability was assessed using baseline and 3-month samples. Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients.Results
Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls. Some biomarkers, including tumor necrosis factor-α and interferon-γ, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period. Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201) of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201) reporting the exacerbation within 30 days of the 3-month visit. CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved.Conclusions
Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD). Further analysis of more promising biomarkers may reveal utility in subsets of patients. Fibrinogen in particular has emerged as a potentially useful biomarker from this cohort and requires further investigation.Trial Registration
SCO104960, clinicaltrials.gov identifier NCT00292552相似文献43.
Mang C. Yu Amos G. Gona Ophelia Gona Suad Al-Rabiai Stanley Von Hagen Edwin Cohen 《Bioelectromagnetics》1993,14(5):449-458
This study was undertaken to determine the effects of extremely low frequency (ELF; 60 Hz) electromagnetic (EM) fields on somatic growth and cortical development, as well as biochemical and morphological maturation, of the rat neopallium. On the fifth day of pregnancy, female rats were put in pairs into plastic cages that were housed in a specially constructed apparatus for irradiation under three separate sets of combination and intensity: 1) 1 kV/m and 10 gauss; 2) 100 kV/m and 1 gauss; and 3) 100 kV/m and 10 gauss. The dams were exposed for 23 h daily, from days 5 through 19 postconception after which they were returned to cages outside the exposure apparatus until they littered. The neonates were culled to eight pups per litter. At 0 (birth), 5, 12, and 19 days postnatally, they were killed for biochemical and morphological studies. Another group of pregnant rats was sham-exposed in an identical apparatus, which was not energized, and the pups were used as controls. The irradiated rats exhibited no physical abnormalities, nor did they show brain deformities such as swelling or herniation following exposure to ELF-EM fields. There was no difference in somatic growth between control and exposed rats, but a small reduction in cortical weight was observed in rats exposed at 1 kV/m and 10 gauss, and 100 kV/m and 1 gauss, respectively. Biochemical measurements of DNA. RNA, protein, and cerebroside concentrations indicated that among the three separate exposures, only the neopallium of rats exposed at 1 kV/m and 10 gauss showed a small reduction in DNA level, as well as small reductions in RNA and protein levels. No changes were noticed in cerebroside levels in any exposed animals, and there were no differences in protein/DNA and cerebroside/DNA ratios between control and exposed rats. Morphological observations did not reveal any detectable alterations in the irradiated rats. These results indicate that exposure to ELF-EM fields caused minimal or no changes in somatic growth and cerebral development of the rat. © 1993 Wiley-Liss, Inc. 相似文献
44.
Amimul M. Ehsan Thomas Geurden Stijn Casaert Sonia M. Parvin Taohidul M. Islam Uddin M. Ahmed Bruno Levecke Jozef Vercruysse Edwin Claerebout 《PloS one》2015,10(2)
Giardia and Cryptosporidium are important causes of diarrhoea in Bangladesh. The high prevalence of both parasites in humans and cattle in rural Bangladesh and the common use of water ponds by village inhabitants and their animals suggest a potential for zoonotic transmission. Direct transmission of Giardia and Cryptosporidium between cattle and their handlers and indirect transmission through water ponds was investigated. Faecal/stool samples were collected from 623 calves and 125 calf handlers in a cross-sectional survey. In two villages, water samples were collected monthly from water ponds and faecal/stool samples were collected monthly from inhabitants and their cattle. Giardia cysts and Cryptosporidium oocysts were detected in water samples and in faecal/stool samples and positive samples were genotyped, to determine their human or animal origin. The prevalence of Giardia and Cryptosporidium in calves was 22% and 5% respectively. In calf handlers, the prevalence of Giardia and Cryptosporidium was 11.2% and 3.2% respectively. Both in the cross-sectional survey and in the longitudinal study in the villages, G. duodenalis assemblage E was most prevalent in calves, while in humans assemblage AII, BIII and BIV were found. In cattle, Cryptosporidium parvum, C. bovis and C. andersoni were identified, but no Cryptosporidium sequences were obtained from humans. Giardia and Cryptosporidium were detected in 14/24 and 12/24 water samples respectively. G. duodenalis assemblage E and BIV (-like), as well as C. andersoni and C. hominis were identified. Although the presence of Giardia and Cryptosporidium in both water ponds suggests that water-borne transmission of Giardia and Cryptosporidium is possible, the genotyping results indicate that there is no significant direct or indirect (water-borne) transmission of Giardia between cattle and people in this area of rural Bangladesh. No conclusions could be drawn for Cryptosporidium, because of the low number of sequences that were obtained from human and water samples. 相似文献
45.
Extensive differential protein phosphorylation as intraerythrocytic Plasmodium falciparum schizonts develop into extracellular invasive merozoites 下载免费PDF全文
Edwin Lasonder Judith L. Green Munira Grainger Gordon Langsley Anthony A. Holder 《Proteomics》2015,15(15):2716-2729
Pathology of the most lethal form of malaria is caused by Plasmodium falciparum asexual blood stages and initiated by merozoite invasion of erythrocytes. We present a phosphoproteome analysis of extracellular merozoites revealing 1765 unique phosphorylation sites including 785 sites not previously detected in schizonts. All MS data have been deposited in the ProteomeXchange with identifier PXD001684 ( http://proteomecentral.proteomexchange.org/dataset/PXD001684 ). The observed differential phosphorylation between extra and intraerythrocytic life‐cycle stages was confirmed using both phospho‐site and phospho‐motif specific antibodies and is consistent with the core motif [K/R]xx[pS/pT] being highly represented in merozoite phosphoproteins. Comparative bioinformatic analyses highlighted protein sets and pathways with established roles in invasion. Within the merozoite phosphoprotein interaction network a subnetwork of 119 proteins with potential roles in cellular movement and invasion was identified and suggested that it is coregulated by a further small subnetwork of protein kinase A (PKA), two calcium‐dependent protein kinases (CDPKs), a phosphatidyl inositol kinase (PI3K), and a GCN2‐like elF2‐kinase with a predicted role in translational arrest and associated changes in the ubquitinome. To test this notion experimentally, we examined the overall ubiquitination level in intracellular schizonts versus extracellular merozoites and found it highly upregulated in merozoites. We propose that alterations in the phosphoproteome and ubiquitinome reflect a starvation‐induced translational arrest as intracellular schizonts transform into extracellular merozoites. 相似文献
46.
Prolactin significantly stimulated protein synthesis rates in a human breast cancer cell line, MCF-7. Total protein per culture also increased to 148% of controls. Proteins precipitated from cell homogenates at pH 4.65 in the presence of calcium ions were resolved by sodium dodecyl sulfate- polyacrylamide gel electrophoresis. The specific radioactivity for almost every polypeptide band increased as a result of protlactin treatment. Cell-type specificity for this prolactin action was indicated by the failure of two other human cell lines (HBL-100 and HEL) to respond similarly. This report is the first demonstration that prolactin has the capability to stimulate general protein synthesis in human breast cancer cells in long-term culture. 相似文献
47.
48.
49.
Woo Jin Kim Alice M Wood Alan F Barker Mark L Brantly Edward J Campbell Edward Eden Gerard McElvaney Stephen I Rennard Robert A Sandhaus James M Stocks James K Stoller Charlie Strange Gerard Turino Edwin K Silverman Robert A Stockley Dawn L DeMeo 《Respiratory research》2012,13(1):16
Background
The development of COPD in subjects with alpha-1 antitrypsin (AAT) deficiency is likely to be influenced by modifier genes. Genome-wide association studies and integrative genomics approaches in COPD have demonstrated significant associations with SNPs in the chromosome 15q region that includes CHRNA3 (cholinergic nicotine receptor alpha3) and IREB2 (iron regulatory binding protein 2).We investigated whether SNPs in the chromosome 15q region would be modifiers for lung function and COPD in AAT deficiency.Methods
The current analysis included 378 PIZZ subjects in the AAT Genetic Modifiers Study and a replication cohort of 458 subjects from the UK AAT Deficiency National Registry. Nine SNPs in LOC123688, CHRNA3 and IREB2 were selected for genotyping. FEV1 percent of predicted and FEV1/FVC ratio were analyzed as quantitative phenotypes. Family-based association analysis was performed in the AAT Genetic Modifiers Study. In the replication set, general linear models were used for quantitative phenotypes and logistic regression models were used for the presence/absence of emphysema or COPD.Results
Three SNPs (rs2568494 in IREB2, rs8034191 in LOC123688, and rs1051730 in CHRNA3) were associated with pre-bronchodilator FEV1 percent of predicted in the AAT Genetic Modifiers Study. Two SNPs (rs2568494 and rs1051730) were associated with the post-bronchodilator FEV1 percent of predicted and pre-bronchodilator FEV1/FVC ratio; SNP-by-gender interactions were observed. In the UK National Registry dataset, rs2568494 was significantly associated with emphysema in the male subgroup; significant SNP-by-smoking interactions were observed.Conclusions
IREB2 and CHRNA3 are potential genetic modifiers of COPD phenotypes in individuals with severe AAT deficiency and may be sex-specific in their impact. 相似文献50.
Yi-Shiang Huang Virginie Bertrand Dimitriya Bozukova Christophe Pagnoulle Christine Labrugère Edwin De Pauw Marie-Claire De Pauw-Gillet Marie-Christine Durrieu 《PloS one》2014,9(12)
Posterior Capsular Opacification (PCO) is the capsule fibrosis developed on implanted IntraOcular Lens (IOL) by the de-differentiation of Lens Epithelial Cells (LECs) undergoing Epithelial Mesenchymal Transition (EMT). Literature has shown that the incidence of PCO is multifactorial including the patient''s age or disease, surgical technique, and IOL design and material. Reports comparing hydrophilic and hydrophobic acrylic IOLs have shown that the former has more severe PCO. On the other hand, we have previously demonstrated that the adhesion of LECs is favored on hydrophobic compared to hydrophilic materials. By combining these two facts and contemporary knowledge in PCO development via the EMT pathway, we propose a biomimetically inspired strategy to promote LEC adhesion without de-differentiation to reduce the risk of PCO development. By surface grafting of a cell adhesion molecule (RGD peptide) onto the conventional hydrophilic acrylic IOL material, the surface-functionalized IOL can be used to reconstitute a capsule-LEC-IOL sandwich structure, which has been considered to prevent PCO formation in literature. Our results show that the innovative biomaterial improves LEC adhesion, while also exhibiting similar optical (light transmittance, optical bench) and mechanical (haptic compression force, IOL injection force) properties compared to the starting material. In addition, compared to the hydrophobic IOL material, our bioactive biomaterial exhibits similar abilities in LEC adhesion, morphology maintenance, and EMT biomarker expression, which is the crucial pathway to induce PCO. The in vitro assays suggest that this biomaterial has the potential to reduce the risk factor of PCO development. 相似文献