全文获取类型
收费全文 | 325篇 |
免费 | 27篇 |
专业分类
352篇 |
出版年
2023年 | 3篇 |
2022年 | 2篇 |
2021年 | 4篇 |
2020年 | 2篇 |
2019年 | 8篇 |
2018年 | 10篇 |
2017年 | 5篇 |
2016年 | 12篇 |
2015年 | 18篇 |
2014年 | 25篇 |
2013年 | 27篇 |
2012年 | 32篇 |
2011年 | 28篇 |
2010年 | 16篇 |
2009年 | 10篇 |
2008年 | 17篇 |
2007年 | 30篇 |
2006年 | 16篇 |
2005年 | 20篇 |
2004年 | 16篇 |
2003年 | 11篇 |
2002年 | 12篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1998年 | 4篇 |
1997年 | 1篇 |
1996年 | 4篇 |
1994年 | 3篇 |
1992年 | 1篇 |
1990年 | 3篇 |
1987年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有352条查询结果,搜索用时 15 毫秒
101.
Anita Maurstad Trine Dale Pål Arne Bjørn 《Human ecology: an interdisciplinary journal》2007,35(5):601-610
Environmental effects of salmon farming are controversial issues. In Northern Norway, cod fishers argue that the location of salmon pens in fjords results in the cessation of local cod spawning. Research supporting or rejecting such statements is scant. There is an absence of both short-term and long-term studies on the effects that salmon farming may have on wild fish stocks. There are few studies of local ecosystem relationships in general. This article explores fishers’ arguments about the effects of salmon farming. It discusses methods of assessing the reliability and validity of fisher knowledge, and contributes to the discussion on assets and limitations of narrative data and experiential knowledge. 相似文献
102.
C-Terminally PEGylated hGH-derivatives 总被引:1,自引:0,他引:1
Peschke B Zundel M Bak S Clausen TR Blume N Pedersen A Zaragoza F Madsen K 《Bioorganic & medicinal chemistry》2007,15(13):4382-4395
A two-step strategy was used for the preparation of C-terminally PEGylated hGH-derivatives. In a first step a CPY-catalyzed transpeptidation was performed on hGH-Leu-Ala, introducing reaction handles, which were used in the second step for the ligation of PEG-moieties. Both oxime-ligation and copper(I) catalyzed [2+3]-cycloaddition reactions were used for the attachment of PEG-moieties. The biological data show a dependency of the potency of the hGH-derivatives on both size as well as shape of the PEG-group. 相似文献
103.
104.
Strong Impact on the Polycyclic Aromatic Hydrocarbon (PAH)-Degrading Community of a PAH-Polluted Soil but Marginal Effect on PAH Degradation when Priming with Bioremediated Soil Dominated by Mycobacteria 下载免费PDF全文
Anders R. Johnsen Stine Schmidt Trine K. Hybholt Sidsel Henriksen Carsten S. Jacobsen Ole Andersen 《Applied microbiology》2007,73(5):1474-1480
Bioaugmentation of soil polluted with polycyclic aromatic hydrocarbons (PAHs) is often disappointing because of the low survival rate and low activity of the introduced degrader bacteria. We therefore investigated the possibility of priming PAH degradation in soil by adding 2% of bioremediated soil with a high capacity for PAH degradation. The culturable PAH-degrading community of the bioremediated primer soil was dominated by Mycobacterium spp. A microcosm containing pristine soil artificially polluted with PAHs and primed with bioremediated soil showed a fast, 100- to 1,000-fold increase in numbers of culturable phenanthrene-, pyrene-, and fluoranthene degraders and a 160-fold increase in copy numbers of the mycobacterial PAH dioxygenase gene pdo1. A nonpolluted microcosm primed with bioremediated soil showed a high rate of survival of the introduced degrader community during the 112 days of incubation. A nonprimed control microcosm containing pristine soil artificially polluted with PAHs showed only small increases in the numbers of culturable PAH degraders and no pdo1 genes. Initial PAH degradation rates were highest in the primed microcosm, but later, the degradation rates were comparable in primed and nonprimed soil. Thus, the proliferation and persistence of the introduced, soil-adapted degraders had only a marginal effect on PAH degradation. Given the small effect of priming with bioremediated soil and the likely presence of PAH degraders in almost all PAH-contaminated soils, it seems questionable to prime PAH-contaminated soil with bioremediated soil as a means of large-scale soil bioremediation. 相似文献
105.
Goll R Gruber F Olsen T Cui G Raschpichler G Buset M Asfeldt AM Husebekk A Florholmen J 《Helicobacter》2007,12(3):185-192
BACKGROUND: Host factors play an important role in the pathophysiology of Helicobacter pylori infection and development of gastritis and related disease. The established opinion is that the T-cell-mediated immune response to H. pylori infection is of Th1 type. Our earlier immune cell phenotype studies indicate a mixed Th1-Th2 profile of the effector cells. Therefore, an extensive adaptive and regulatory cytokine gene expression profile was conducted by quantitative real-time polymerase chain reaction (qPCR). MATERIALS AND METHODS: Biopsies from gastric mucosa of 91 patients diagnosed as H. pylori negative, H. pylori positive with gastritis, or H. pylori positive with peptic ulcer were obtained by endoscopy. Gene expressions of nine cytokines and CagA status were measured by qPCR. RESULTS: All cytokine genes showed higher expression levels in the presence of H. pylori when compared to H. pylori-negative samples (fold increase: IL8: x 11.2; IL12A: x 2.4; TNF-alpha: x 5.2; IFN-gamma: x 4.3; IL4: x 3.6; IL6: x 14.7; and IL10: x 6.7). Patients infected with CagA-positive strains had higher expression of IL1-beta and IL18 compared to patients infected with CagA-negative strains (x 1.6 for IL1-beta and x 2.0 for IL18). Patients with duodenal ulcer had a lower antral Th1/Th2 ratio than other H. pylori-positive patients. CONCLUSIONS: The cytokine profile of H. pylori-infected gastric mucosa shows a mixed Th1-Th2 profile. Furthermore, a high IL10 expression may indicate that also regulatory T cells play a role in the chronic phase of H. pylori infection. 相似文献
106.
Heidi de Wit Susanne Schöning Trine L Toft‐Bertelsen Juliane Lauks Iwona Ziomkiewicz Annita N Weiss Alexander Schulz Gabriele Fischer von Mollard Matthijs Verhage Jakob B Sørensen 《The EMBO journal》2014,33(15):1681-1697
The SNARE protein vti1a is proposed to drive fusion of intracellular organelles, but recent data also implicated vti1a in exocytosis. Here we show that vti1a is absent from mature secretory vesicles in adrenal chromaffin cells, but localizes to a compartment near the trans‐Golgi network, partially overlapping with syntaxin‐6. Exocytosis is impaired in vti1a null cells, partly due to fewer Ca2+‐channels at the plasma membrane, partly due to fewer vesicles of reduced size and synaptobrevin‐2 content. In contrast, release kinetics and Ca2+‐sensitivity remain unchanged, indicating that the final fusion reaction leading to transmitter release is unperturbed. Additional deletion of the closest related SNARE, vti1b, does not exacerbate the vti1a phenotype, and vti1b null cells show no secretion defects, indicating that vti1b does not participate in exocytosis. Long‐term re‐expression of vti1a (days) was necessary for restoration of secretory capacity, whereas strong short‐term expression (hours) was ineffective, consistent with vti1a involvement in an upstream step related to vesicle generation, rather than in fusion. We conclude that vti1a functions in vesicle generation and Ca2+‐channel trafficking, but is dispensable for transmitter release. 相似文献
107.
Trine P Ludvigsen Niels Wiinberg Christina J Jensen Annemette T Callesen Regitze W Andersen Anne Sofie H J?rgensen Berit ? Christoffersen Henrik D Pedersen Sophia G Moesgaard Lisbeth H Olsen 《Comparative medicine》2014,64(6):471-477
Few methods for noninvasive assessment of arterial stiffness and endothelial dysfunction in porcine models are available. The aim of this study was to evaluate methods for assessment of arterial stiffness and endothelial dysfunction in anesthetized Göttingen minipigs. Pulse-wave velocity (PWV) was assessed in male Göttingen minipigs (n = 8; age approximately 60 wk) by using applanation tonometry of the carotid and femoral arteries. In addition, flow-mediated vasodilation (FMD) was assessed by using vascular ultrasonography of the brachial artery to evaluate endothelial dysfunction. To evaluate the reproducibility of the methods, minipigs were anesthetized by intravenous infusion of ketamine and midazolam and examined every other day for a total of 3 trials. Neither examination day nor systolic, diastolic, or mean arterial blood pressure statistically influenced PWV or FMD. The median interexamination coefficient of variation was 17% for PWV and 59% for FMD. Measured values of PWV corresponded largely to those in clinically healthy humans, but FMD values were lower than expected for lean, young animals. Although the ketamine–midazolam anesthesia we used has been associated with minor hemodynamic effects in vivo, in vitro studies suggest that both drugs are vasodilatory. Therefore anesthesia might have influenced the endothelial response, contributing to the modest FMD response and the concurrent high coefficients of variation that we noted. We conclude that PWV—but not FMD—showed acceptable interexamination variation for its potential application in porcine models.Abbreviations: FMD, flow-mediated vasodilation; FVI, integrated flow velocity; GTN, glyceryl trinitrate; PWV, pulse-wave velocity; T, transit timeCardiovascular disease has become a global challenge in public health,42 and the development and characterization of comparative animal models are of increasing importance. Several animal models of atherosclerosis, including porcine, have been described.11,12,34 Due to similarities to humans in the anatomy of the cardiovascular system and metabolic physiology, pigs represent a generally useful model in regard to preclinical evaluation and pharmacology.36 Assessment of changes related to atherosclerosis in vivo would be valuable in for example longitudinal assessment of drug effect, but few noninvasive methods for evaluating structural and functional changes in the arteries of pigs are available. In humans, increased arterial stiffness, which occurs with advanced age, also is caused by the pathophysiologic changes associated with atherosclerosis,26 and noninvasive methods for assessing arterial stiffness have been established. The evaluation of pulse-wave velocity (PWV) by using pressure transducers, such as applanation tonometry, is a method recognized as an independent predictor for cardiovascular events in epidemiologic studies.21 The method evaluates the velocity with which the pulse wave is propagated through the arterial tree, with arterial stiffness causing increased velocity.1,22,29,37,39 Flow-mediated vasodilation (FMD), assessed by vascular ultrasonography, represents a noninvasive evaluation of endothelial-dependent vasodilation. A decrease in vasodilation as a response to increased shear stress has been recognized as a marker of endothelial dysfunction, which precedes the development of atherosclerosis.5,7 Recent studies have shown that the FMD method is applicable in large animals (that is, dogs and horses) and that a decreased FMD response occurs in dogs with valvular heart disease.10,15,23,28The aim of this study was to evaluate the reproducibility of methods for assessing arterial stiffness (PWV) and endothelial function (FMD response) in anesthetized Göttingen minipigs, including the influences of arterial blood pressure, heart rate, and room and body temperatures on these methods. 相似文献
108.
Trine Ostergaard Nielsen Lennart Friis-Hansen Steen Seier Poulsen Birgitte Federspiel Boe Sandahl Sorensen 《PloS one》2014,9(4)
Gastric cancer is a major cause of cancer-related deaths in both men and women. The epidermal growth factor receptors are EGFR, HER2, HER3 and HER4. Of the four epidermal growth factor receptors, EGFR and HER2 are well-known oncogenes involved in gastric cancer. Little, however, is known about the role played by HER3 and HER4 in this disease. We obtained paired samples from the tumor and the adjacent normal tissue from the same patient undergoing surgery for gastric cancer. Using RT-qPCR, we quantified the mRNA expression of the four receptors including the HER4 splicing isoforms and all the ligands activating these receptors. Using immunohistochemistry, the protein expression of HER4 was also quantified. We found that HER2 mRNA expression was upregulated in the tumor tissue compared to the matched normal tissue (p = 0.0520). All ligands with affinity for EGFR were upregulated, whereas the expression of EGFR was unchanged. Interestingly, we found the mRNA expression of HER4 (p = 0.0002) and its ligand NRG4 (p = 0.0009) to be downregulated in the tumor tissue compared to the matched normal tissue. HER4 downregulation was demonstrated for all the alternatively spliced isoforms of this receptor. These results support the involvement of EGFR and HER2 in gastric cancer and suggest an interesting association of reduced HER4 expression with development of gastric cancer. 相似文献
109.
Ingrid Kristine Ohm Erhe Gao Maria Belland Olsen Katrine Alfsnes Marte Bliks?en Jonas ?gaard Trine Ranheim St?le Haugset Nymo Yangchen Dhondup Holmen P?l Aukrust Arne Yndestad Leif Erik Vinge 《PloS one》2014,9(8)
Aim
Myocardial infarction (MI) remains a major cause of death and disability worldwide, despite available reperfusion therapies. Inflammatory signaling is considered nodal in defining final infarct size. Activation of the innate immune receptor toll-like receptors (TLR) 9 prior to ischemia and reperfusion (I/R) reduces infarct size, but the consequence of TLR9 activation timed to the onset of ischemia is not known.Methods and Results
The TLR9-agonist; CpG B was injected i.p. in C57BL/6 mice immediately after induction of ischemia (30 minutes). Final infarct size, as well as area-at-risk, was measured after 24 hours of reperfusion. CpG B injection resulted in a significant increase in circulating granulocytes and monocytes both in sham and I/R mice. Paradoxically, clear evidence of reduced cardiac infiltration of both monocytes and granulocytes could be demonstrated in I/R mice treated with CpG B (immunocytochemistry, myeloperoxidase activity and mRNA expression patterns). In addition, systemic TLR9 activation elicited significant alterations of cardiac inflammatory genes. Despite these biochemical and cellular changes, there was no difference in infarct size between vehicle and CpG B treated I/R mice.Conclusion
Systemic TLR9-stimulation upon onset of ischemia and subsequent reperfusion does not alter final infarct size despite causing clear alterations of both systemic and cardiac inflammatory parameters. Our results question the clinical usefulness of TLR9 activation during cardiac I/R. 相似文献110.