全文获取类型
收费全文 | 165篇 |
免费 | 13篇 |
专业分类
178篇 |
出版年
2021年 | 1篇 |
2020年 | 1篇 |
2017年 | 2篇 |
2016年 | 3篇 |
2015年 | 9篇 |
2014年 | 4篇 |
2013年 | 17篇 |
2012年 | 15篇 |
2011年 | 7篇 |
2010年 | 6篇 |
2009年 | 6篇 |
2008年 | 6篇 |
2007年 | 4篇 |
2006年 | 11篇 |
2005年 | 5篇 |
2004年 | 8篇 |
2003年 | 4篇 |
2002年 | 7篇 |
2001年 | 6篇 |
2000年 | 9篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有178条查询结果,搜索用时 15 毫秒
91.
Rydning A Lyng O Adamsen BL Falkmer S Sandvik AK Grønbech JE 《American journal of physiology. Gastrointestinal and liver physiology》2001,280(6):G1061-G1069
Acid back diffusion into the rat stomach mucosa leads to gastric vasodilation. We hypothesized that histamine, if released from the rat mucosa under such conditions, is mast cell derived and involved in the vasodilator response. Gastric blood flow (GBF) and luminal histamine were measured in an ex vivo chamber. Venous histamine was measured from totally isolated stomachs. Mucosal mast cells (MMC), submucosal connective tissue mast cells (CTMC), and chromogranin A-immunoreactive cells (CgA IR) were assessed morphometrically. After mucosal exposure to 1.5 M NaCl, the mucosa was subjected to saline at pH 5.5 (control) or pH 1.0 (H(+) back diffusion) for 60 min. H(+) back diffusion evoked a marked gastric hyperemia, increase of luminal and venous histamine, and decreased numbers of MMC and CTMC. CgA IR cells were not influenced. Depletion of mast cells with dexamethasone abolished (and stabilization of mast cells with ketotifen attenuated) both hyperemia and histamine release in response to H(+) back diffusion. GBF responses to H(+) back diffusion were attenuated by H(1) and abolished by H(3) but not H(2) receptor blockers. Our data conform to the idea that mast cells are involved in the gastric hyperemic response to acid back diffusion via release of histamine. 相似文献
92.
Two Genes That Map to the STSL Locus Cause Sitosterolemia: Genomic Structure and Spectrum of Mutations Involving Sterolin-1 and Sterolin-2, Encoded by ABCG5 and ABCG8, Respectively 总被引:12,自引:0,他引:12 下载免费PDF全文
Kangmo Lu Mi-Hye Lee Starr Hazard Angela Brooks-Wilson Hideki Hidaka Hideto Kojima Leiv Ose Anton F. H. Stalenhoef Tatu Mietinnen Ingemar Bjorkhem Eric Bruckert Arti Pandya H. Bryan Brewer ?Jr. Gerald Salen Michael Dean Anand Srivastava Shailendra B. Patel 《American journal of human genetics》2001,69(2):278-290
Sitosterolemia is a rare autosomal recessive disorder characterized by (a) intestinal hyperabsorption of all sterols, including cholesterol and plant and shellfish sterols, and (b) impaired ability to excrete sterols into bile. Patients with this disease have expanded body pools of cholesterol and very elevated plasma plant-sterol species and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. In previous studies, we have mapped the STSL locus to human chromosome 2p21. Recently, we reported that a novel member of the ABC-transporter family, named "sterolin-1" and encoded by ABCG5, is mutated in 9 unrelated families with sitosterolemia; in the remaining 25 families, no mutations in sterolin-1 could be identified. We identified another ABC transporter, located <400 bp upstream of sterolin-1, in the opposite orientation. Mutational analyses revealed that this highly homologous protein, termed "sterolin-2" and encoded by ABCG8, is mutated in the remaining pedigrees. Thus, two highly homologous genes, located in a head-to-head configuration on chromosome 2p21, are involved as causes of sitosterolemia. These studies indicate that both sterolin-1 and sterolin-2 are indispensable for the regulation of sterol absorption and excretion. Identification of sterolin-1 and sterolin-2 as critical players in the regulation of dietary-sterol absorption and excretion identifies a new pathway of sterol transport. 相似文献
93.
Streptococcus pneumoniae and probably most other members of the genus Streptococcus are competent for natural genetic transformation. During the competent state, S. pneumoniae produces a murein hydrolase, CbpD, that kills and lyses noncompetent pneumococci and closely related species. Previous studies have shown that CbpD is essential for efficient transfer of genomic DNA from noncompetent to competent cells in vitro. Consequently, it has been proposed that CbpD together with the cognate immunity protein ComM constitutes a DNA acquisition mechanism that enables competent pneumococci to capture homologous DNA from closely related streptococci sharing the same habitat. Although genes encoding CbpD homologs or CbpD-related proteins are present in many different streptococcal species, the genomes of a number of streptococci do not encode CbpD-type proteins. In the present study we show that the genomes of nearly all species lacking CbpD encode an unrelated competence-regulated murein hydrolase termed LytF. Using Streptococcus gordonii as a model system, we obtained evidence indicating that LytF is a functional analogue of CbpD. In sum, our results show that a murein hydrolase gene is part of the competence regulon of most or all streptococcal species, demonstrating that these muralytic enzymes constitute an essential part of the streptococcal natural transformation system. 相似文献
94.
An anatomy of interactions among species in a seasonal world 总被引:1,自引:0,他引:1
Mathematical models merging biological and predictable seasonal dynamics were used to simulate four types of organism interactions: competition, prey-predation, mutualism and facilitation. By analysing trajectories for biomass in phase portraits (i.e. species 1 biomass plotted against species 2 biomass) graphically and numerically, we found that each of the four interaction types showed characteristic patterns ("fingerprints") in phase space. All the four interaction types could be distinguished, even though their time trajectories were strongly modified by seasonal forces. For each of the interaction types, we were able to identify characteristics of the interaction that most strongly distinguished it from the others. We could also assess the relative effect of species characteristics and seasonality on each of the four interactions. The simulations indicate that prey-predation is strongly influenced by seasonal forces and by the characteristics of the predator and its prey. A system variability index got a high value (SVI)=0.167 relative to those of the other interaction types (competition 0.01, mutualism 0.007 and facilitation 0.005). The result was obtained by calculating, angles between successive vectors linking pairs of samples and the positive x-axis and arranging these as frequency histograms for each of the four quadrants of the phase portrait. In an effort to capture circular motions and other characteristics of the trajectories sampled, angle frequencies were analysed using multivariate statistics (PCA), yielding "characteristic directions" in phase space. We believe that the characteristic patterns identified also will be found in real time series. 相似文献
95.
We studied the frequency of partial albinism amongst hooded crows in Norway, mostly in a population at Trondheim. A total of 3461 birds were collected from the field. About 5% of fledged young showed albinoid markings on their third right-hand primary; the frequency decreased to 2% among yearling birds and to only 1% among birds that had acquired their adult plumage. No significant difference was found in relation to sex. The partially albinoid birds were typically small-sized, both as regards their bone structure (ulna, tibia, tarsus) and feathers (wing, tail). Their feathers bore more defective markings than those of birds of normal plumage coloration. A study of the plumage of preserved specimens of hooded crows in the collections of Natural History museums in Norway also indicated that a differential mortality takes place in the wild, such albinoid birds disappearing rapidly from the population.
Experimental interchanges of eggs and hatchlings between nests indicated that the occurrence of partial albinism may be related to the feeding conditions during the nestling stage, rather than to any genetical differences. It is not known, however, whether the former was due to starvation, to an unbalanced diet, or to eating poisonous food. 相似文献
Experimental interchanges of eggs and hatchlings between nests indicated that the occurrence of partial albinism may be related to the feeding conditions during the nestling stage, rather than to any genetical differences. It is not known, however, whether the former was due to starvation, to an unbalanced diet, or to eating poisonous food. 相似文献
96.
97.
Torkil Benterud Leonid Pankratov R?nnaug Solberg Nils Bolstad Anders Skinningsrud Lars Baumbusch Leiv Sandvik Ola Didrik Saugstad 《PloS one》2015,10(10)
Objective
Total tau (T-tau), phosphorylated tau (p-Tau) and Beta-Amyloid 1–42 (AB42) in Cerebrospinal Fluid (CSF) are useful biomarkers in neurodegenerative diseases. The aim of the study was to investigate the role of these and other CSF biomarkers (T-tau, p-Tau, AB42, S100B and NSE), during hypoxia-reoxygenation in a newborn pig model.Design
Thirty newborn pigs were included in a study of moderate or severe hypoxia. The moderate hypoxia group (n = 12) was exposed to global hypoxia (8% O2) until Base excess (BE) reached -15 mmol/l. The pigs in the group exposed to severe hypoxia (n = 12) received 8% O2 until BE reached -20 mmol/l or mean Blood Pressure fell below 20 mm Hg, The control group (n = 6) was kept at room air. For all treatments, the CSF was collected at 9.5 hours after the intervention.Results
The level of AB42 in CSF was significantly lower in the pigs exposed to severe hypoxia compared with the control group, 922(SD +/-445)pg/ml versus. 1290(SD +/-143) pg/ml (p<0.05), respectively. Further, a non-significant reduction of AB42 was observed in the group exposed to moderate hypoxia T-tau and p-Tau revealed no significant differences between the intervention groups and the control group, however a significantly higher level of S100B was seen in the CSF of pigs receiving hypoxia in comparison to the level in the control group. Further on, there was a moderate negative correlation between the levels of AB42 and S100B in CSF, as well as a moderate negative correlation between Lactate in blood at end of hypoxia and AB42 in CSF.Interpretation
This is the first study to our knowledge that demonstrated a significant drop in AB42 in CSF after neonatal hypoxia. Whether or not this has an etiological basis for adult neurodegenerative disorders needs to be studied with additional experiments and epidemiological studies. AB42 and S100B are significantly changed in neonatal pigs subjected to hypoxia compared to controls and thus may be valuable biomarkers of perinatal asphyxia. 相似文献98.
Helene Kolstad Skovdahl Atle van Beelen Granlund Ann Elisabet ?stvik Torunn Bruland Ingunn Bakke Sverre Helge Torp Jan Kristian Dam?s Arne Kristian Sandvik 《PloS one》2015,10(11)
Background
The chemokine CCL20 and its receptor CCR6 are putative drug targets in inflammatory bowel disease, and CCL20 is a novel IBD predilection gene. Previous findings on the CCL20 response in these diseases are divergent. This study was undertaken to examine CCL20 and CCR6 during active and inactive disease, and mechanisms for CCL20 regulation by the innate immune system. As TLR3 has recently emerged as a possible mediator of CCL20 production, we hypothesised that this TLR plays an important role in enterocytic CCL20 production.Methods
A large microarray study on colonic pinch biopsies from active and inactive ulcerative colitis and Crohn’s disease provided background information. CCL20 and CCR6 were localized and their expression levels assessed in biopsies using in situ hybridization and immunohistochemistry. Regulation of CCL20 was studied in the HT29 cell line using a panel of pattern recognition receptor ligands followed by a TLR3 siRNA assay.Results
CCL20 and CCR6 mRNA abundances were increased during active inflammation (CCL20 5.4-fold in ulcerative colitis and 4.2-fold in Crohn’s disease; CCR6 1.8 and 2.0, respectively). CCL20 and CCR6 mRNA positive immune cells in lamina propria were more numerous, and CCL20 immunoreactivity increased massively in the epithelial cells during active inflammation for both diseases. TLR3 stimulation potently induced upregulation and release of CCL20 from HT29 cells, and TLR3 silencing reduced CCL20 mRNA and protein levels.Conclusions
The CCL20-CCR6 axis is involved during active inflammation in both ulcerative colitis and Crohn’s disease. The epithelial cells seem particularly involved in the CCL20 response, and results from this study strongly suggest that the innate immune system is important for activation of the epithelium, especially through TLR3. 相似文献99.
Turid Omland Harriet Akre Kathrine A. Lie Peter Jebsen Leiv Sandvik Kjell Br?ndbo 《PloS one》2014,9(11)
In this cohort study we examined whether gender, age at onset, observation time or human papillomavirus (HPV) genotype are risk factors for an aggressive clinical course in Recurrent Respiratory Papillomatosis (RRP). Clinical data from patient records comprised gender, age at onset, date of first endolaryngeal procedure with biopsy, date of last follow-up, total number of endolaryngeal procedures, and complications during the observation period. Disease was defined as juvenile (JoRRP) or adult onset (AoRRP) according to whether the disease was acquired before or after the age of 18. Aggressive disease was defined as distal spread, tracheostomy, four surgical operations annually or >10 surgeries in total. DNA was extracted from formalin-fixed paraffin-embedded tissue. HPV genotyping was performed by quantitative PCR assay identifying 15 HPV genotypes. The study included 224 patients. The majority were males (141/174 in AoRRPs and 31/50 in JoRRPs; p = 0.005). The median follow-up from initial diagnosis was 12.0 years (IQR 3.7–32.9) for JoRRPs and 4.0 years (IQR 0.8–11.7) for AoRRPs. The disease was more aggressive in juveniles than adults (p<0.001), a difference that disappeared after 10 years'' observation. JoRRPs with aggressive disease were younger at onset (mean difference 4.6 years, 95%CI [2.4, 6.8], p = 0.009). HPV6 or −11 was present in all HPV-positive papillomas. HPV11 was more prevalent in aggressive disease, and HPV6 in non-aggressive disease (p<0.001). Multiple logistic regression revealed that only age at onset (OR = 0.69, 95% CI [0.53, 0.88], p = 0.003) was associated with aggressive disease in juveniles, while HPV11 (OR = 3.74, 95% CI [1.40, 9.97], p = 0.008) and observation time >10 years (OR = 13.41, 95% CI [5.46, 32.99[, p<001) were risk factors in adults. In conclusion, the only significant risk factor for developing aggressive disease in JoRRPs was age at onset, but both HPV11 and observation time >10 years were risk factors for an aggressive disease course in AoRRPs. 相似文献
100.
Kari Helene Berg Gro Anita Stams?s Daniel Straume Leiv Sigve H?varstein 《Journal of bacteriology》2013,195(19):4342-4354
Streptococcus pneumoniae produces two class B penicillin-binding proteins, PBP2x and PBP2b, both of which are essential. It is generally assumed that PBP2x is specifically involved in septum formation, while PBP2b is dedicated to peripheral cell wall synthesis. However, little experimental evidence exists to substantiate this belief. In the present study, we obtained evidence that strongly supports the view that PBP2b is essential for peripheral peptidoglycan synthesis. Depletion of PBP2b expression gave rise to long chains of cells in which individual cells were compressed in the direction of the long axis and looked lentil shaped. This morphological change is consistent with a role for pneumococcal PBP2b in the synthesis of the lateral cell wall. Depletion of PBP2x, on the other hand, resulted in lemon-shaped and some elongated cells with a thickened midcell region. Low PBP2b levels gave rise to changes in the peptidoglycan layer that made pneumococci sensitive to exogenously added LytA during logarithmic growth and refractory to chain dispersion upon addition of LytB. Interestingly, analysis of the cell wall composition of PBP2b-depleted pneumococci revealed that they had a larger proportion of branched stem peptides in their peptidoglycan than the corresponding undepleted cells. Furthermore, MurM-deficient mutants, i.e., mutants lacking the ability to synthesize branched muropeptides, were found to require much higher levels of PBP2b to sustain growth than those required by MurM-proficient strains. These findings might help to explain why increased incorporation of branched muropeptides is required for high-level beta-lactam resistance in S. pneumoniae. 相似文献