全文获取类型
收费全文 | 843篇 |
免费 | 61篇 |
专业分类
904篇 |
出版年
2023年 | 9篇 |
2022年 | 10篇 |
2021年 | 27篇 |
2020年 | 23篇 |
2019年 | 18篇 |
2018年 | 31篇 |
2017年 | 34篇 |
2016年 | 43篇 |
2015年 | 31篇 |
2014年 | 48篇 |
2013年 | 55篇 |
2012年 | 51篇 |
2011年 | 48篇 |
2010年 | 34篇 |
2009年 | 29篇 |
2008年 | 28篇 |
2007年 | 35篇 |
2006年 | 21篇 |
2005年 | 23篇 |
2004年 | 33篇 |
2003年 | 29篇 |
2002年 | 24篇 |
2001年 | 17篇 |
2000年 | 17篇 |
1999年 | 8篇 |
1998年 | 6篇 |
1995年 | 4篇 |
1994年 | 8篇 |
1992年 | 7篇 |
1991年 | 11篇 |
1990年 | 6篇 |
1989年 | 5篇 |
1988年 | 10篇 |
1987年 | 7篇 |
1986年 | 11篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1982年 | 9篇 |
1981年 | 8篇 |
1980年 | 6篇 |
1979年 | 10篇 |
1978年 | 4篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1974年 | 7篇 |
1973年 | 4篇 |
1969年 | 4篇 |
1968年 | 6篇 |
1966年 | 5篇 |
排序方式: 共有904条查询结果,搜索用时 15 毫秒
141.
Ilse M. Boudewijn Alen Faiz Katrina Steiling Erica van der Wiel Eef D. Telenga Susan J. M. Hoonhorst Nick H. T. ten Hacken Corry-Anke Brandsma Huib A. M. Kerstjens Wim Timens Irene H. Heijink Marnix R. Jonker Harold G. de Bruin J. Sebastiaan Vroegop Henk R. Pasma Wim G. Boersma Pascal Wielders Frank van den Elshout Khaled Mansour Avrum Spira Marc E. Lenburg Victor Guryev Dirkje S. Postma Maarten van den Berge 《Respiratory research》2017,18(1):213
Background
Nasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium.Methods
Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls.Results
In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate?<?0.01). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDRGSEA <?0.001).Conclusion
We identified a nasal gene expression profile that differentiates severe COPD patients from controls. Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus. These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD.Trial registration
ClinicalTrials.gov registration number NCT01351792 (registration date May 10, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 19, 2009), ClinicalTrials.gov registration number NCT00807469 (registration date December 11, 2008).142.
Objective
To evaluate the in vitro effects of different concentrations of ivermectin and/or artemether on Fasciolagigantica worms and to study the parasitological changes and tegumental alterations using scanning electron microscopy (SEM).Methods
Fasciola gigantica worms were incubated in vitro for 24 and 48 h with three concentrations of either ivermectin or artemether (10, 20 and 50 μg/ml) or both in half concentration of either (5, 10 and 25 μg/ml).Results
Exposure of Fasciola worms to 25 + 25 μg/ml of combined drug regimens or to 50 μg/ml of either ivermectin or artemether for 48 h led to 100%, 41.7% and 75% worm killing which were accompanied by a significant reduction in egg laying capacity and significant increase in dead eggs maximally recorded in combined drug regimens. SEM of the flukes incubated for 48 h with combined drug regimens showed maximal tegumental disruption with swelling of the worm body, roughness, blebbing, sloughing and complete loss of spines. Disruption to the tegument of the flukes induced by artemether was more than that of ivermectin.Conclusions
Artemether alone or combined with ivermectin in half doses had potent fasciocidal activities. Besides, half doses of combined drug regimens had higher ovicidal effects than each drug alone. In vivo studies are recommended to explore the efficacy of combined regimens against Fasciola infection. 相似文献143.
144.
145.
146.
Release Mechanisms Behind Polysaccharides-Based Famotidine Controlled Release Matrix Tablets 总被引:1,自引:0,他引:1
Enas M. Elmowafy Gehanne A. S. Awad Samar Mansour Abd El-Hamid A. El-Shamy 《AAPS PharmSciTech》2008,9(4):1230-1239
Polysaccharides, which have been explored to possess gelling properties and a wide margin of safety, were used to formulate
single-unit floating matrix tablets by a direct compression technique. This work has the aim to allow continuous slow release
of famotidine above its site of absorption. The floating approach was achieved by the use of the low density polypropylene
foam powder. Polysaccharides (κ-carrageenan, gellan gum, xyloglucan, and pectin) and blends of polysaccharides (κ-carrageenan
and gellan gum) and cellulose ethers (hydroxypropylmethyl cellulose, hydroxypropylcellulose, sodium carboxymethyl cellulose)
were tried to modulate the release characteristics. The prepared floating tablets were evaluated for their floating behavior,
matrix integrity, swelling studies, in vitro drug release studies, and kinetic analysis of the release data. The differential scanning calorimetry and Fourier transform
infrared spectroscopy studies revealed that changing the polymer matrix system by formulation of polymers blends resulted
in formation of molecular interactions which may have implications on drug release characteristics. This was obvious from
the retardation in drug release and change in its mechanistics. 相似文献
147.
Rahbar Mohammad Reza Zarei Mahboubeh Jahangiri Abolfazl Khalili Saeed Nezafat Navid Negahdaripour Manica Fattahian Yaser Ghasemi Younes 《International journal of peptide research and therapeutics》2020,26(3):1269-1282
International Journal of Peptide Research and Therapeutics - Acinetobacter baumannii is an important pathogen responsible for nosocomial infections worldwide. Trimeric autotransporters, the... 相似文献
148.
Twelve randomly-selected isolates of Fusarium graminearum that produce 3-acetyl-deoxynivalenol (3-ADON) or 15-acetyl-deoxynivalenol (15-ADON) were screened by thin-layer chromatography
(TLC) for their ability to produce ADON and zearalenone (ZEA) mycotoxins when grown on water agar containing different concentrations
of sucrose. The results showed the ability of the F. graminearum 3-ADON chemotype population to produce DON and ZEA at a lower concentration range of sucrose (5-7%) compared with the 15-ADON
chemotype (30-40%). The former distinction allows for sucrose-water agar to be employed as a rapid and simple differential
medium, where two separate sucrose-gradient concentrations discriminate 3-ADON from 15-ADON populations. In the light of the
shift in sugar concentrations occurring during the process of grain formation and maturation, the difference in mycotoxin
production between the two populations is discussed with respect to predicting Fusarium head blight (FHB) epidemiology and
accumulation of DON and ZEA. 相似文献
149.
F. C. Connell P. Ostergaard C. Carver G. Brice N. Williams S. Mansour P. S. Mortimer Steve Jeffery Lymphoedema Consortium 《Human genetics》2009,124(6):625-631
Milroy disease (hereditary lymphoedema type I, MIM 153100) is a congenital onset primary lymphoedema with autosomal dominant
inheritance. Mutations in the gene, vascular endothelial growth factor receptor 3, VEGFR3 (FLT4), are known to cause Milroy disease, but there is uncertainty about the prevalence of VEGFR3 mutations in patients with primary lymphoedema and more specifically in those with a phenotype that resembles Milroy disease.
This study aims to address this issue and thereby delineate the Milroy disease phenotype. Fifty-two patients with primary
lymphoedema were analysed for mutations in the coding regions of VEGFR3. Patients were divided into four groups: Typical Milroy disease with family history (group I), typical Milroy disease with
no family history (group II), atypical Milroy disease (group III), and complex primary lymphoedema (group IV). Results demonstrated
that with rigorous phenotyping the likelihood of detecting VEGFR3 mutations is optimised. Mutation prevalence is 75% in typical Milroy patients with a family history (group I) and 68% if
positive family history is not a diagnostic criterion. A positive family history is not essential in Milroy disease. The likelihood
of detecting VEGFR3 mutations in patients who have a phenotype which is not typical of Milroy disease is very small (<5%). For the 22 mutation
positive patients, 14 novel VEGFR3 mutations were identified, two of which were in exon 22 and one in exon 17, confirming that these exons should be included
in VEGFR3 analysis. No mutations were found outside the kinase domains, showing that analysis of this part of the gene is not useful
for Milroy disease patients. VEGFC, which encodes the ligand for VEGFR3, was sequenced in all patients with typical Milroy disease (groups I and II) and no
mutations were identified.
F. C. Connell and P. Ostergaard contributed equally to this work.
An erratum to this article can be found at 相似文献
150.
Mansour Djedaini Milou-Daniel Drici Perla Saint-Marc Annie Ladoux 《Biochemical and biophysical research communications》2009,386(1):96-100
HIV-protease inhibitors (PIs) markedly decreased mortality of HIV-infected patients. However, their use has been associated with occurence of metabolic abnormalities the causes of which are not well understood. We report here that lopinavir, one of the most prescribed PI, dose-dependently co-induced insulin resistance and ER stress in human adipocytes obtained from differentiation of precursor cells.Insulin resistance was subsequent to IRS1 phosphorylation defects and resulted in a concentration-dependent decrease of glucose uptake. The major ER stress pathway involved was the phosphorylation of eIF2-α. Salubrinal, a selective eIF2-α dephosphorylation inhibitor, induced insulin resistance by targeting IRS1 phosphorylation at serine 312 and acted synergistically with LPV when both drugs were used in combination.This study points out the key role of eIF2-α phosphorylation in the development of PI-associated insulin resistance and ER stress. Thus, this protein represents a promising therapeutic target for development of new PIs devoid of adverse metabolic effects. 相似文献