全文获取类型
收费全文 | 2360篇 |
免费 | 139篇 |
国内免费 | 1篇 |
专业分类
2500篇 |
出版年
2024年 | 7篇 |
2023年 | 36篇 |
2022年 | 80篇 |
2021年 | 122篇 |
2020年 | 52篇 |
2019年 | 61篇 |
2018年 | 90篇 |
2017年 | 65篇 |
2016年 | 104篇 |
2015年 | 112篇 |
2014年 | 117篇 |
2013年 | 169篇 |
2012年 | 162篇 |
2011年 | 162篇 |
2010年 | 97篇 |
2009年 | 83篇 |
2008年 | 104篇 |
2007年 | 94篇 |
2006年 | 91篇 |
2005年 | 76篇 |
2004年 | 85篇 |
2003年 | 66篇 |
2002年 | 59篇 |
2001年 | 42篇 |
2000年 | 30篇 |
1999年 | 18篇 |
1998年 | 20篇 |
1997年 | 16篇 |
1996年 | 9篇 |
1995年 | 15篇 |
1994年 | 8篇 |
1993年 | 12篇 |
1992年 | 15篇 |
1991年 | 16篇 |
1990年 | 8篇 |
1989年 | 7篇 |
1988年 | 14篇 |
1986年 | 11篇 |
1985年 | 14篇 |
1984年 | 9篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1979年 | 9篇 |
1978年 | 12篇 |
1977年 | 9篇 |
1976年 | 9篇 |
1974年 | 9篇 |
1973年 | 10篇 |
1969年 | 9篇 |
1968年 | 6篇 |
排序方式: 共有2500条查询结果,搜索用时 0 毫秒
11.
Yvonne Raatz Saleh Ibrahim Marc Feldmann Ewa M Paleolog 《Arthritis research & therapy》2012,14(4):R169
Introduction
Dysregulated angiogenesis is implicated in the pathogenesis of rheumatoid arthritis (RA). To provide a more profound understanding of arthritis-associated angiogenesis, we evaluated the expression of angiogenesis-modulating genes at onset, peak and declining phases of collagen-induced arthritis (CIA), a well-established mouse model for RA.Methods
CIA was induced in DBA/1 mice with type II collagen. Functional capillary density in synovial tissue of knee joints was determined by intravital fluorescence microscopy. To assess the ability of arthritic joint homogenates to induce angiogenesis, an endothelial chemotaxis assay and an in vivo matrigel plug assay were employed. The temporal expression profile of angiogenesis-related genes in arthritic paws was analysed by quantitative real-time RT-PCR using an angiogenesis focused array as well as gene specific PCR. Finally, we investigated the therapeutic effect of a monoclonal antibody specifically blocking the binding of VEGF to neuropilin (NRP)-1.Results
Although arthritic paw homogenates displayed angiogenic activity in vitro and in vivo, and synovia of arthritic paws appeared highly vascularised on histological examination, the functional capillary density in arthritic knee synovia was significantly decreased, whereas capillary diameter was increased. Of the 84 genes analysed, 41 displayed a differential expression in arthritic paws as compared to control paws. Most significant alterations were seen at the peak of clinical arthritis. Increased mRNA expression could be observed for VEGF receptors (Flt-1, Flk-1, Nrp-1, Nrp-2), as well as for midkine, hepatocyte growth factor, insulin-like growth factor-1 and angiopoietin-1. Signalling through NRP-1 accounted in part for the chemotactic activity for endothelial cells observed in arthritic paw homogenates. Importantly, therapeutic administration of anti-NRP1B antibody significantly reduced disease severity and progression in CIA mice.Conclusions
Our findings confirm that the arthritic synovium in murine CIA is a site of active angiogenesis, but an altered balance in the expression of angiogenic factors seems to favour the formation of non-functional and dilated capillaries. Furthermore, our results validate NRP-1 as a key player in the pathogenesis of CIA, and support the VEGF/VEGF receptor pathway as a potential therapeutic target in RA. 相似文献12.
Irum Sidra Andleeb Saadia Ali Amjad Rashid Muhammad Ibrahim Majid Mahnoor 《International journal of peptide research and therapeutics》2021,27(4):2313-2331
International Journal of Peptide Research and Therapeutics - Pseudomonas aeruginosa (P. aeruginosa) is a critical healthcare challenge due to its ability to cause persistent infections and the... 相似文献
13.
14.
15.
R. John Dobbs Sylvia M. Dobbs Clive Weller ré Charlett Ingvar T. Bjarnason Alan Curry David S. Ellis Mohammad A. A. Ibrahim Maria V. McCrossan John O'Donohue Robert J. Owen Norman L. Oxlade Ashley B. Price Jeremy D. Sanderson Malur Sudhanva John Williams 《Helicobacter》2008,13(5):309-322
We challenge the concept of idiopathic parkinsonism (IP) as inevitably progressive neurodegeneration, proposing a natural history of sequential microbial insults with predisposing host response. Proof-of-principle that infection can contribute to IP was provided by case studies and a placebo-controlled efficacy study of Helicobacter eradication. "Malignant" IP appears converted to "benign", but marked deterioration accompanies failure. Similar benefit on brady/hypokinesia from eradicating "low-density" infection favors autoimmunity. Although a minority of UK probands are urea breath test positive for Helicobacter , the predicted probability of having the parkinsonian label depends on the serum H. pylori antibody profile, with clinically relevant gradients between this "discriminant index" and disease burden and progression. In IP, H. pylori antibodies discriminate for persistently abnormal bowel function, and specific abnormal duodenal enterocyte mitochondrial morphology is described in relation to H. pylori infection. Slow intestinal transit manifests as constipation from the prodrome. Diarrhea may flag secondary small-intestinal bacterial overgrowth. This, coupled with genetically determined intense inflammatory response, might explain evolution from brady/hypokinetic to rigidity-predominant parkinsonism. 相似文献
16.
Dietmar B?nsch Ralph Schneider Ibrahim Akin Cristoph A. Nienaber 《Journal of visualized experiments : JoVE》2012,(60)
Implantable cardioverter-defibrillators (ICDs) terminate ventricular tachycardia (VT) and ventricular fibrillation (VF) with high efficacy and can protect patients from sudden cardiac death (SCD). However, inappropriate shocks may occur if tachycardias are misdiagnosed. Inappropriate shocks are harmful and impair patient quality of life. The risk of inappropriate therapy increases with lower detection rates programmed in the ICD. Single-chamber detection poses greater risks for misdiagnosis when compared with dual-chamber devices that have the benefit of additional atrial information. However, using a dual-chamber device merely for the sake of detection is generally not accepted, since the risks associated with the second electrode may outweigh the benefits of detection. Therefore, BIOTRONIK developed a ventricular lead called the LinoxSMART S DX, which allows for the detection of atrial signals from two electrodes positioned at the atrial part of the ventricular electrode. This device contains two ring electrodes; one that contacts the atrial wall at the junction of the superior vena cava (SVC) and one positioned at the free floating part of the electrode in the atrium. The excellent signal quality can only be achieved by a special filter setting in the ICD (Lumax 540 and 740 VR-T DX, BIOTRONIK). Here, the ease of implantation of the system will be demonstrated. 相似文献
17.
Adnan A. Bekhit Eskedar T. Lodebo Ariaya Hymete Hanan M. Ragab Salma A. Bekhit Kikuko Amagase Afnan Batubara Mohammed A. S. Abourehab Alaa El-Din A. Bekhit Tamer M. Ibrahim 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):2320
Promising inhibitory activities of the parasite multiplication were obtained upon evaluation of in vivo antimalarial activities of new pyrazolylpyrazoline derivatives against Plasmodium berghei infected mice. Further evaluation of 5b and 6a against chloroquine-resistant strain (RKL9) of P. falciparum showed higher potency than chloroquine. In vitro antileishmanial activity testing against Leishmania aethiopica promastigote and amastigote forms indicated that 5b, 6a and 7b possessed promising activity compared to miltefosine and amphotericin B deoxycholate. Moreover, antileishmanial activity reversal of the active compounds via folic and folinic acids showed comparable results to the positive control trimethoprim, indicating an antifolate mechanism via targeting leishmanial DHFR and PTR1. The compounds were non-toxic at 125, 250 and 500 mg/kg. In addition, docking of the most active compound against putative malarial target Pf-DHFR-TS and leishmanial PTR1 rationalised the observed activities. Molecular dynamics simulations confirmed a stable and high potential binding of 7a against leishmanial PTR1. 相似文献
18.
Water buffalo lactoperoxidase (WBLP) was purified with Amberlite CG 50 H+ resin, CM Sephadex C-50 ion-exchange chromatography, and Sephadex G-100 gel filtration chromatography from skim milk. All purification steps of the WBLP were shown with SDS-PAGE and Rz (A412/A280) controlled the purification degree of the enzyme. Rz value for the purified WBLP was 0.8. To determine purification steps and kinetic properties, the activity of enzyme was measured by using 2,2-azino-bis-(3-ethylbenzthiazoline-6 sulfonic acid) diammonium salt (ABTS) as a choromogenic substrate at pH=6. Km, Vmax, optimum pH, and optimum temperature for the WBLP were found by means of graphics for ABTS as substrates. Optimum pH and optimum temperature of the WBLP were 6 and 60 degrees C, respectively. Km value at optimum pH and optimum temperature for the WBLP was 0.82 mM. Vmax value at optimum pH and optimum temperature was 13.7 micromol/mL x min. Km value at optimum pH and 25 degrees C for the WBLP was 0.77 mM. Vmax value at optimum pH and 25 degrees C was 4.83 micromol/mL x min. The purified WBLP was found to have high antibacterial activity in a thiocynate-H2O2 medium for some pathogenic bacteria, such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginose, Shigella sonnei, Staphylococcus saphrophyticus, Staphylococcus epidermidis, and Shigella dysenteriae and compared with well known antibacterial substances such as tetracycline, penicillin, and netilmicine. 相似文献
19.
Ibrahim M. El-Deen El-Zend Manar A. Tantawy Mohamed A. Barakat Lamiaa A. A. 《Russian Journal of Bioorganic Chemistry》2022,48(2):380-390
Russian Journal of Bioorganic Chemistry - A series of coumarin and aza-coumarin derivatives (II–IX) were synthesized and identified using IR, 1H NMR, and 13C NMR spectral data. All the... 相似文献
20.