全文获取类型
收费全文 | 213篇 |
免费 | 49篇 |
国内免费 | 1篇 |
出版年
2017年 | 3篇 |
2016年 | 5篇 |
2015年 | 6篇 |
2014年 | 4篇 |
2013年 | 7篇 |
2012年 | 10篇 |
2011年 | 7篇 |
2010年 | 11篇 |
2009年 | 9篇 |
2008年 | 7篇 |
2007年 | 13篇 |
2006年 | 6篇 |
2005年 | 11篇 |
2004年 | 10篇 |
2003年 | 7篇 |
2002年 | 8篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 9篇 |
1997年 | 6篇 |
1996年 | 5篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1980年 | 2篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1968年 | 4篇 |
1965年 | 2篇 |
1957年 | 2篇 |
1953年 | 2篇 |
1951年 | 2篇 |
1950年 | 2篇 |
1944年 | 2篇 |
排序方式: 共有263条查询结果,搜索用时 15 毫秒
21.
Abstract. 1. Stage-specific survival and recruitment of spruce budworm were measured by frequent sampling of foliage in four outbreak populations over a 15-year period in Ontario and Quebec, Canada.
2. Patterns of change in population density during the outbreak collapse phase were closely linked to changes in survival of the late immature stages, and were determined largely by the impact of natural enemies.
3. Host-plant feedback also contributed significantly to survival patterns throughout the outbreak: annual defoliation influenced survival of fourth and fifth instars and fecundity while cumulative defoliation influenced survival of the very early larval stages (first and second) via impacts on stand condition.
4. Inclusion of this host-plant feedback reveals spruce budworm population dynamics as a function of density-related trophic interactions that vary in their order and strength of influence over time. This view re-introduces the importance of forest interactions as a component of dynamics of the spruce budworm. 相似文献
2. Patterns of change in population density during the outbreak collapse phase were closely linked to changes in survival of the late immature stages, and were determined largely by the impact of natural enemies.
3. Host-plant feedback also contributed significantly to survival patterns throughout the outbreak: annual defoliation influenced survival of fourth and fifth instars and fecundity while cumulative defoliation influenced survival of the very early larval stages (first and second) via impacts on stand condition.
4. Inclusion of this host-plant feedback reveals spruce budworm population dynamics as a function of density-related trophic interactions that vary in their order and strength of influence over time. This view re-introduces the importance of forest interactions as a component of dynamics of the spruce budworm. 相似文献
22.
Alexandra S. Solovyova Jonathan A. Pointon Paul R. Race Wendy D. Smith Michael A. Kehoe Mark J. Banfield 《European biophysics journal : EBJ》2010,39(3):469-480
Adhesion of the serotype M1 Streptococcus pyogenes strain SF370 to human tonsil explants and cultured keratinocytes requires extended polymeric surface structures called pili.
In this important human pathogen, pili are assembled from three protein subunits: Spy0125, Spy0128 and Spy0130 through the
action of sortase enzymes. For this study, the structural properties of these pili proteins have been investigated in solution.
Spy0125 and Spy0128 display characteristics of globular, folded proteins. Circular dichroism suggests a largely β-sheet composition
for Spy0128 and Spy0125; Spy0130 appears to contain little secondary structure. Each of the proteins adopts a monodisperse,
monomeric state in solution as assessed by analytical ultracentrifugation. Further, small-angle X-ray scattering curves for
Spy0125, Spy0128 and Spy0130 suggest each protein adopts an elongated shape, likely comprised of two domains, with similar
maximal dimensions. Based on the scattering data, dummy atom models of each of the pili subunits have been reconstructed ab
initio. This study provides the first insights into the structure of Streptococcus pyogenes minor pili subunits, and possible implications for protein function are discussed. 相似文献
23.
Resistance to chronic wasting disease in transgenic mice expressing a naturally occurring allelic variant of deer prion protein
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Meade-White K Race B Trifilo M Bossers A Favara C Lacasse R Miller M Williams E Oldstone M Race R Chesebro B 《Journal of virology》2007,81(9):4533-4539
Prion protein (PrP) is a required factor for susceptibility to transmissible spongiform encephalopathy or prion diseases. In transgenic mice, expression of prion protein (PrP) from another species often confers susceptibility to prion disease from that donor species. For example, expression of deer or elk PrP in transgenic mice has induced susceptibility to chronic wasting disease (CWD), the prion disease of cervids. In the current experiments, transgenic mice expressing two naturally occurring allelic variants of deer PrP with either glycine (G) or serine (S) at residue 96 were found to differ in susceptibility to CWD infection. G96 mice were highly susceptible to infection, and disease appeared starting as early as 160 days postinfection. In contrast, S96 mice showed no evidence of disease or generation of disease-associated protease-resistant PrP (PrPres) over a 600-day period. At the time of clinical disease, G96 mice showed typical vacuolar pathology and deposition of PrPres in many brain regions, and in some individuals, extensive neuronal loss and apoptosis were noted in the hippocampus and cerebellum. Extraneural accumulation of PrPres was also noted in spleen and intestinal tissue of clinically ill G96 mice. These results demonstrate the importance of deer PrP polymorphisms in susceptibility to CWD infection. Furthermore, this deer PrP transgenic model is the first to demonstrate extraneural accumulation of PrPres in spleen and intestinal tissue and thus may prove useful in studies of CWD pathogenesis and transmission by oral or other natural routes of infection. 相似文献
24.
The goal of this study was to provide material property data for the cement/bone composite resulting from the introduction of PMMA bone cement into human vertebral bodies. A series of quasistatic tensile and compressive mechanical tests were conducted using cement/bone composite structures machined from cement-infiltrated vertebral bodies. Experiments were performed both at room temperature and at body temperature. We found that the modulus of the composite structures was lower than bulk cement (p<0.0001). For compression at 37( composite function)C: composite =2.3+/-0.5GPa, cement =3.1+/-0.2GPa; at 23( composite function)C: composite =3.0+/-0.3GPa, cement =3.4+/-0.2GPa. Specimens tested at room temperature were stiffer than those tested at body temperature (p=0.0004). Yield and ultimate strength factors for the composite were all diminished (55-87%) when compared to cement properties. In general, computational models have assumed that cement/bone composite had the same modulus as cement. The results of this study suggest that computational models of cement infiltrated vertebrae and cemented arthroplasties could be improved by specifying different material properties for cement and cement/bone composite. 相似文献
25.
Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hart CE Race V Achouri Y Wiame E Sharrard M Olpin SE Watkinson J Bonham JR Jaeken J Matthijs G Van Schaftingen E 《American journal of human genetics》2007,80(5):931-937
We present the first two identified cases of phosphoserine aminotransferase deficiency. This disorder of serine biosynthesis has been identified in two siblings who showed low concentrations of serine and glycine in plasma and cerebrospinal fluid. Clinically, the index patient presented with intractable seizures, acquired microcephaly, hypertonia, and psychomotor retardation and died at age 7 mo despite supplementation with serine (500 mg/kg/d) and glycine (200 mg/kg/d) from age 11 wk. The younger sibling received treatment from birth, which led to a normal outcome at age 3 years. Measurement of phosphoserine aminotransferase activity in cultured fibroblasts in the index patient was inconclusive, but mutational analysis revealed compound heterozygosity for two mutations in the PSAT1 gene--one frameshift mutation (c.delG107) and one missense mutation (c.299A-->C [p.Asp100Ala])--in both siblings. Expression studies of the p.Asp100Ala mutant protein revealed a V(max) of only 15% of that of the wild-type protein. 相似文献
26.
L. DA S. PONTES J.-F. SOUSSANA† F. LOUAULT D. ANDUEZA‡ P. CARRÈRE 《Functional ecology》2007,21(5):844-853
27.
Moreau M Rialland P Pelletier JP Martel-Pelletier J Lajeunesse D Boileau C Caron J Frank D Lussier B del Castillo JR Beauchamp G Gauvin D Bertaim T Thibaud D Troncy E 《Arthritis research & therapy》2011,13(3):R98-13
Introduction
The aim of this prospective, randomized, controlled, double-blind study was to evaluate the effects of tiludronate (TLN), a bisphosphonate, on structural, biochemical and molecular changes and function in an experimental dog model of osteoarthritis (OA).Methods
Baseline values were established the week preceding surgical transection of the right cranial/anterior cruciate ligament, with eight dogs serving as OA placebo controls and eight others receiving four TLN injections (2 mg/kg subcutaneously) at two-week intervals starting the day of surgery for eight weeks. At baseline, Week 4 and Week 8, the functional outcome was evaluated using kinetic gait analysis, telemetered locomotor actimetry and video-automated behaviour capture. Pain impairment was assessed using a composite numerical rating scale (NRS), a visual analog scale, and electrodermal activity (EDA). At necropsy (Week 8), macroscopic and histomorphological analyses of synovium, cartilage and subchondral bone of the femoral condyles and tibial plateaus were assessed. Immunohistochemistry of cartilage (matrix metalloproteinase (MMP)-1, MMP-13, and a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS5)) and subchondral bone (cathepsin K) was performed. Synovial fluid was analyzed for inflammatory (PGE2 and nitrite/nitrate levels) biomarkers. Statistical analyses (mixed and generalized linear models) were performed with an α-threshold of 0.05.Results
A better functional outcome was observed in TLN dogs than OA placebo controls. Hence, TLN dogs had lower gait disability (P = 0.04 at Week 8) and NRS score (P = 0.03, group effect), and demonstrated behaviours of painless condition with the video-capture (P < 0.04). Dogs treated with TLN demonstrated a trend toward improved actimetry and less pain according to EDA. Macroscopically, both groups had similar level of morphometric lesions, TLN-treated dogs having less joint effusion (P = 0.01), reduced synovial fluid levels of PGE2 (P = 0.02), nitrites/nitrates (P = 0.01), lower synovitis score (P < 0.01) and a greater subchondral bone surface (P < 0.01). Immunohistochemical staining revealed lower levels in TLN-treated dogs of MMP-13 (P = 0.02), ADAMTS5 (P = 0.02) in cartilage and cathepsin K (P = 0.02) in subchondral bone.Conclusion
Tiludronate treatment demonstrated a positive effect on gait disability and joint symptoms. This is likely related to the positive influence of the treatment at improving some OA structural changes and reducing the synthesis of catabolic and inflammatory mediators. 相似文献28.
29.
Foulquier F Amyere M Jaeken J Zeevaert R Schollen E Race V Bammens R Morelle W Rosnoblet C Legrand D Demaegd D Buist N Cheillan D Guffon N Morsomme P Annaert W Freeze HH Van Schaftingen E Vikkula M Matthijs G 《American journal of human genetics》2012,91(1):15-26
Protein glycosylation is a complex process that depends not only on the activities of several enzymes and transporters but also on a subtle balance between vesicular Golgi trafficking, compartmental pH, and ion homeostasis. Through a combination of autozygosity mapping and expression analysis in two siblings with an abnormal serum-transferrin isoelectric focusing test (type 2) and a peculiar skeletal phenotype with epiphyseal, metaphyseal, and diaphyseal dysplasia, we identified TMEM165 (also named TPARL) as a gene involved in congenital disorders of glycosylation (CDG). The affected individuals are homozygous for a deep intronic splice mutation in TMEM165. In our cohort of unsolved CDG-II cases, we found another individual with the same mutation and two unrelated individuals with missense mutations in TMEM165. TMEM165 encodes a putative transmembrane 324 amino acid protein whose cellular functions are unknown. Using a siRNA strategy, we showed that TMEM165 deficiency causes Golgi glycosylation defects in HEK cells. 相似文献
30.
目的:分别克隆人细小病毒B19三个主要蛋白VP1、VP2、NS1全长基因,构建真核表达载体。方法:利用PCR和分子克隆技术,分别将B19病毒vp1、vp2、ns1基因全长片段扩增后,构建带荧光标签的真核表达载体;在人体细胞中表达并通过荧光、RT-PCR和Western Blot、测序等方法鉴定。结果:成功构建了包含B19病毒vp1、vp2、ns1全长基因,并在人体细胞中表达了VP1、VP2、NS1蛋白。结论:人微小病毒B19三个主要蛋白基因得到克隆和表达,为进行相关的研究奠定了基础。 相似文献