全文获取类型
收费全文 | 956篇 |
免费 | 68篇 |
国内免费 | 3篇 |
专业分类
1027篇 |
出版年
2024年 | 4篇 |
2023年 | 32篇 |
2022年 | 47篇 |
2021年 | 77篇 |
2020年 | 85篇 |
2019年 | 117篇 |
2018年 | 68篇 |
2017年 | 47篇 |
2016年 | 55篇 |
2015年 | 38篇 |
2014年 | 70篇 |
2013年 | 80篇 |
2012年 | 67篇 |
2011年 | 61篇 |
2010年 | 37篇 |
2009年 | 29篇 |
2008年 | 25篇 |
2007年 | 18篇 |
2006年 | 15篇 |
2005年 | 15篇 |
2004年 | 5篇 |
2003年 | 6篇 |
2002年 | 5篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1968年 | 2篇 |
排序方式: 共有1027条查询结果,搜索用时 9 毫秒
11.
Kowalczuk L Touchard E Omri S Jonet L Klein C Valamanes F Berdugo M Bigey P Massin P Jeanny JC Behar-Cohen F 《PloS one》2011,6(3):e17462
Objective
There are controversies regarding the pro-angiogenic activity of placental growth factor (PGF) in diabetic retinopathy (DR). For a better understanding of its role on the retina, we have evaluated the effect of a sustained PGF over-expression in rat ocular media, using ciliary muscle electrotransfer (ET) of a plasmid encoding rat PGF-1 (pVAX2-rPGF-1).Materials and Methods
pVAX2-rPGF-1 ET in the ciliary muscle (200 V/cm) was achieved in non diabetic and diabetic rat eyes. Control eyes received saline or naked plasmid ET. Clinical follow up was carried out over three months using slit lamp examination and fluorescein angiography. After the control of rPGF-1 expression, PGF-induced effects on retinal vasculature and on the blood-external barrier were evaluated respectively by lectin and occludin staining on flat-mounts. Ocular structures were visualized through histological analysis.Results
After fifteen days of rPGF-1 over-expression in normal eyes, tortuous and dilated capillaries were observed. At one month, microaneurysms and moderate vascular sprouts were detected in mid retinal periphery in vivo and on retinal flat-mounts. At later stages, retinal pigmented epithelial cells demonstrated morphological abnormalities and junction ruptures. In diabetic retinas, PGF expression rose between 2 and 5 months, and, one month after ET, rPGF-1 over-expression induced glial activation and proliferation.Conclusion
This is the first demonstration that sustained intraocular PGF production induces vascular and retinal changes similar to those observed in the early stages of diabetic retinopathy. PGF and its receptor Flt-1 may therefore be looked upon as a potential regulatory target at this stage of the disease. 相似文献12.
Secondary Metabolites Produced by the Marine Bacterium Halobacillus salinus That Inhibit Quorum Sensing-Controlled Phenotypes in Gram-Negative Bacteria 下载免费PDF全文
Margaret E. Teasdale Jiayuan Liu Joselynn Wallace Fatemeh Akhlaghi David C. Rowley 《Applied microbiology》2009,75(3):567-572
Certain bacteria use cell-to-cell chemical communication to coordinate community-wide phenotypic expression, including swarming motility, antibiotic biosynthesis, and biofilm production. Here we present a marine gram-positive bacterium that secretes secondary metabolites capable of quenching quorum sensing-controlled behaviors in several gram-negative reporter strains. Isolate C42, a Halobacillus salinus strain obtained from a sea grass sample, inhibits bioluminescence production by Vibrio harveyi in cocultivation experiments. With the use of bioassay-guided fractionation, two phenethylamide metabolites were identified as the active agents. The compounds additionally inhibit quorum sensing-regulated violacein biosynthesis by Chromobacterium violaceum CV026 and green fluorescent protein production by Escherichia coli JB525. Bacterial growth was unaffected at concentrations below 200 μg/ml. Evidence is presented that these nontoxic metabolites may act as antagonists of bacterial quorum sensing by competing with N-acyl homoserine lactones for receptor binding. 相似文献
13.
14.
Mohyeddin Mandana Bonab Kamran Alimoghaddam Fatemeh Talebian Syed Hamid Ghaffari Ardeshir Ghavamzadeh Behrouz Nikbin 《BMC cell biology》2006,7(1):14-7
Background
A hot new topic in medical treatment is the use of mesenchymal stem cells (MSC) in therapy. The low frequency of this subpopulation of stem cells in bone marrow (BM) necessitates their in vitro expansion prior to clinical use. We evaluated the effect of long term culture on the senescence of these cells. 相似文献15.
Fatemeh Adelnia Ceereena Ubaida‐Mohien Ruin Moaddel Michelle Shardell Alexey Lyashkov Kenneth W. Fishbein Miguel A. Aon Richard G. Spencer Luigi Ferrucci 《Aging cell》2020,19(4)
Adequate support of energy for biological activities and during fluctuation of energetic demand is crucial for healthy aging; however, mechanisms for energy decline as well as compensatory mechanisms that counteract such decline remain unclear. We conducted a discovery proteomic study of skeletal muscle in 57 healthy adults (22 women and 35 men; aged 23–87 years) to identify proteins overrepresented and underrepresented with better muscle oxidative capacity, a robust measure of in vivo mitochondrial function, independent of age, sex, and physical activity. Muscle oxidative capacity was assessed by 31P magnetic resonance spectroscopy postexercise phosphocreatine (PCr) recovery time (τPCr) in the vastus lateralis muscle, with smaller τPCr values reflecting better oxidative capacity. Of the 4,300 proteins quantified by LC‐MS in muscle biopsies, 253 were significantly overrepresented with better muscle oxidative capacity. Enrichment analysis revealed three major protein clusters: (a) proteins involved in key energetic mitochondrial functions especially complex I of the electron transport chain, tricarboxylic acid (TCA) cycle, fatty acid oxidation, and mitochondrial ABC transporters; (b) spliceosome proteins that regulate mRNA alternative splicing machinery, and (c) proteins involved in translation within mitochondria. Our findings suggest that alternative splicing and mechanisms that modulate mitochondrial protein synthesis are central features of the molecular mechanisms aimed at maintaining mitochondrial function in the face of impairment. Whether these mechanisms are compensatory attempt to counteract the effect of aging on mitochondrial function should be further tested in longitudinal studies. 相似文献
16.
Fatemeh Farshchi Mohammad Hasanzadeh Ahad Mokhtarzadeh 《Journal of molecular recognition : JMR》2020,33(4)
In this study, a novel electroconductive interface was prepared based on Fe3O4 magnetic nanoparticle and cysteamine functionalized gold nanoparticle. The engineered interface was used as signal amplification substrate in the electrochemical analysis of antibody‐antigen binding. For this purpose, biotinilated‐anti‐prostate‐specific antigen (PSA) antibody was bioconjugated with iron oxide magnetic nanoparticles (Fe3O4) and drop‐casted on the surface of glassy carbon electrode (GCE). Also, secondary antibody (HRP‐Ab2) encapsulated on gold nanoparticles caped by cysteamine was immobilized on the surface of GCE modified electrode. A transmission electron microscopy images shows that a sandwich immunoreaction was done and binding of Ab1 and Ab2 performed successfully. Various parameters of immunoassay, including the loading of magnetic nanoparticles, the amount of gold nanoparticle conjugate, and the immunoreaction time, were optimized. The detection limit of 0.001 μg. L?1 of PSA was obtained under optimum experimental conditions. It is found that such magneto‐bioassay could be readily used for simultaneous parallel detection of multiple proteins by using multiple inorganic metal nanoparticle tracers and are expected to open new opportunities for early stage diagnosis of cancer in near future. 相似文献
17.
Mehrabi Fatemeh Shamspur Tayebeh Sheibani Hassan Mostafavi Ali Mohamadi Maryam Hakimi Hamid Bahramabadi Reza Salari Elham 《Biometals》2021,34(6):1237-1246
BioMetals - Trimethoprim and sulfamethoxazole are prescribed for a broad spectrum of bacteria. However, the use of these medicines is restricted due to the risk of microbial resistance in the body.... 相似文献
18.
Malihe Keramati Farzin Roohvand Mohammad Mehdi Aslani Fatemeh Motevalli Shohreh khatami Arash Memarnejadian 《Journal of industrial microbiology & biotechnology》2013,40(1):151-158
Streptokinase (SK), the heterogeneous protein family secreted by some groups of β-hemolytic streptococci (βHS), is a plasminogen activator and well-known drug for thrombolytic therapy. Differences in plasminogen activation property of streptococcal culture supernatants (SCS) have been traditionally used to identify superior producer strains and SK genes (skc) for recombinant SK (rSK) production. However, the role of SK heterogeneity and whether SK activities in SCS correlate with that of their corresponding rSK is a matter of debate. To address these concerns, SCS of nine group C streptococci (GCS) screened among 252 βHS clinical isolates were compared for plasminogen activation using S-2251 chromogenic assay. The GCS (Streptococcus equisimilis) showing the highest (GCS-S87) and lowest (GCS-S131) activities were selected for PCR-based isolation of skc, cloning and rSK production in Escherichia coli. The 6×His-tagged rSK proteins were purified by NI–NTA chromatography, analyzed by SDS-PAGE and Western blotting and their activities were determined. While SCS of GCS-S87 and GCS-S131 showed different plasminogen activations (95 and 35 %, respectively) compared to that of the reference strain (GCS-9542), but interestingly rSK of all three strains showed close specific activities (1.33, 1.70, and 1.55 × 104 IU mg?1). Accordingly, SKS87 and SKS131 had more than 90 % sequence identity at the amino acids level compared to SK9542. Therefore, SK heterogeneity by itself may not contribute to the differences in plasminogen activation properties of SCS and evaluation of this activity in SCS might not be a proper assay for screening superior skc. 相似文献
19.
Noushin Saljoughian Tahereh Taheri Farnaz Zahedifard Yasaman Taslimi Fatemeh Doustdari Azam Bolhassani Delaram Doroud Hiva Azizi Kazem Heidari Mohammad Vasei Nabiollah Namvar Asl Barbara Papadopoulou Sima Rafati 《PLoS neglected tropical diseases》2013,7(4)
Visceral leishmaniasis (VL) is a vector-borne disease affecting humans and domestic animals that constitutes a serious public health problem in many countries. Although many antigens have been examined so far as protein- or DNA-based vaccines, none of them conferred complete long-term protection. The use of the lizard non-pathogenic to humans Leishmania (L.) tarentolae species as a live vaccine vector to deliver specific Leishmania antigens is a recent approach that needs to be explored further. In this study, we evaluated the effectiveness of live vaccination in protecting BALB/c mice against L. infantum infection using prime-boost regimens, namely Live/Live and DNA/Live. As a live vaccine, we used recombinant L. tarentolae expressing the L. donovani A2 antigen along with cysteine proteinases (CPA and CPB without its unusual C-terminal extension (CPB-CTE)) as a tri-fusion gene. For DNA priming, the tri-fusion gene was encoded in pcDNA formulated with cationic solid lipid nanoparticles (cSLN) acting as an adjuvant. At different time points post-challenge, parasite burden and histopathological changes as well as humoral and cellular immune responses were assessed. Our results showed that immunization with both prime-boost A2-CPA-CPB-CTE-recombinant L. tarentolae protects BALB/c mice against L. infantum challenge. This protective immunity is associated with a Th1-type immune response due to high levels of IFN-γ production prior and after challenge and with lower levels of IL-10 production after challenge, leading to a significantly higher IFN-γ/IL-10 ratio compared to the control groups. Moreover, this immunization elicited high IgG1 and IgG2a humoral immune responses. Protection in mice was also correlated with a high nitric oxide production and low parasite burden. Altogether, these results indicate the promise of the A2-CPA-CPB-CTE-recombinant L. tarentolae as a safe live vaccine candidate against VL. 相似文献
20.
Mohammadi Ali Akbar Zarei Ahmad Esmaeilzadeh Marjan Taghavi Mahmoud Yousefi Mahmood Yousefi Zahra Sedighi Fatemeh Javan Safoura 《Biological trace element research》2020,195(1):343-352
Biological Trace Element Research - Heavy metal pollution of soils in industrial zones continues to attract attention because of its potential human health risks. The present research is an attempt... 相似文献