全文获取类型
收费全文 | 344篇 |
免费 | 31篇 |
专业分类
375篇 |
出版年
2023年 | 2篇 |
2022年 | 6篇 |
2021年 | 5篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 6篇 |
2016年 | 5篇 |
2015年 | 15篇 |
2014年 | 18篇 |
2013年 | 13篇 |
2012年 | 31篇 |
2011年 | 26篇 |
2010年 | 10篇 |
2009年 | 13篇 |
2008年 | 17篇 |
2007年 | 23篇 |
2006年 | 21篇 |
2005年 | 14篇 |
2004年 | 4篇 |
2003年 | 5篇 |
2002年 | 7篇 |
2001年 | 8篇 |
2000年 | 8篇 |
1999年 | 10篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 5篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1983年 | 6篇 |
1982年 | 4篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 3篇 |
1970年 | 2篇 |
1968年 | 4篇 |
1960年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有375条查询结果,搜索用时 15 毫秒
181.
Damian Paul Drew Nadja Krichau Kirsten Reichwald Henrik Toft Simonsen 《Phytochemistry Reviews》2009,8(3):581-599
The guaianolide group of sesquiterpene lactones contains a large number of compounds with biological activity. One of these
guaianolides, thapsigargin from the genus Thapsia (Apiaceae), has been a subject of particular interest in recent years because of its ability to induce apoptosis, as the
active part of a pro-drug, has produced promising results for the targeted treatment of prostate cancer. In this review, recent
advances in understanding the biosynthetic pathway of sesquiterpenes in plants is described with a special emphasis on guaianolides,
and a hypothetical pathway for the biosynthesis of thapsigargin is presented. Eighty-seven guaianolides from Apiaceae are
presented. These compounds provide clues to possible enzymatic mechanisms generating the guaianolides in Apiaceae. Some of
these 87 compounds have proven or might prove interesting with regards to their biological activity. 相似文献
182.
Neural adaptation to resistance training: changes in evoked V-wave and H-reflex responses. 总被引:5,自引:0,他引:5
Per Aagaard Erik B Simonsen Jesper L Andersen Peter Magnusson Poul Dyhre-Poulsen 《Journal of applied physiology》2002,92(6):2309-2318
Combined V-wave and Hoffmann (H) reflex measurements were performed during maximal muscle contraction to examine the neural adaptation mechanisms induced by resistance training. The H-reflex can be used to assess the excitability of spinal alpha-motoneurons, while also reflecting transmission efficiency (i.e., presynaptic inhibition) in Ia afferent synapses. Furthermore, the V-wave reflects the overall magnitude of efferent motor output from the alpha-motoneuron pool because of activation from descending central pathways. Fourteen male subjects participated in 14 wk of resistance training that involved heavy weight-lifting exercises for the muscles of the leg. Evoked V-wave, H-reflex, and maximal M-wave (M(max)) responses were recorded before and after training in the soleus muscle during maximal isometric ramp contractions. Maximal isometric, concentric, and eccentric muscle strength was measured by use of isokinetic dynamometry. V-wave amplitude increased approximately 50% with training (P < 0.01) from 3.19 +/- 0.43 to 4.86 +/- 0.43 mV, or from 0.308 +/- 0.048 to 0.478 +/- 0.034 when expressed relative to M(max) (+/- SE). H-reflex amplitude increased approximately 20% (P < 0.05) from 5.37 +/- 0.41 to 6.24 +/- 0.49 mV, or from 0.514 +/- 0.032 to 0.609 +/- 0.025 when normalized to M(max). In contrast, resting H-reflex amplitude remained unchanged with training (0.503 +/- 0.059 vs. 0.499 +/- 0.063). Likewise, no change occurred in M(max) (10.78 +/- 0.86 vs. 10.21 +/- 0.66 mV). Maximal muscle strength increased 23-30% (P < 0.05). In conclusion, increases in evoked V-wave and H-reflex responses were observed during maximal muscle contraction after resistance training. Collectively, the present data suggest that the increase in motoneuronal output induced by resistance training may comprise both supraspinal and spinal adaptation mechanisms (i.e., increased central motor drive, elevated motoneuron excitability, reduced presynaptic inhibition). 相似文献
183.
Anna K. Simonsen Luke G. Barrett Peter H. Thrall Suzanne M. Prober 《Ecology letters》2019,22(12):2077-2086
A pervasive challenge in microbial ecology is understanding the genetic level where ecological units can be differentiated. Ecological differentiation often occurs at fine genomic levels, yet it is unclear how to utilise ecological information to define ecotypes given the breadth of environmental variation among microbial taxa. Here, we present an analytical framework that infers clusters along genome‐based microbial phylogenies according to shared environmental responses. The advantage of our approach is the ability to identify genomic clusters that best fit complex environmental information whilst characterising cluster niches through model predictions. We apply our method to determine climate‐associated ecotypes in populations of nitrogen‐fixing symbionts using whole genomes, explicitly sampled to detect climate differentiation across a heterogeneous landscape. Although soil and plant host characteristics strongly influence distribution patterns of inferred ecotypes, our flexible statistical method enabled us to identify climate‐associated genomic clusters using environmental data, providing solid support for ecological specialisation in soil symbionts. 相似文献
184.
Amyloid adhesins are abundant in natural biofilms 总被引:2,自引:0,他引:2
Larsen P Nielsen JL Dueholm MS Wetzel R Otzen D Nielsen PH 《Environmental microbiology》2007,9(12):3077-3090
Surface-associated amyloid fibrils have been described by bacteria in the family Enterbacteriaceae, but it is unknown to what extent amyloid adhesins are present in natural biofilms. In this study, amyloid adhesins were specifically stained with Thioflavin T and two conformationally specific antibodies targeting amyloid fibrils. These three independent detection methods were each combined with fluorescence in situ hybridization using fluorescently labelled oligonucleotide probes in order to link phenotype with identity. Escherichia coli mutants with and without amyloid adhesins (curli) served as controls. In biofilms from four different natural habitats, bacteria producing extracellular amyloid adhesins were identified within several phyla: Proteobacteria (Alpha-, Beta-, Gamma- and Deltaproteobacteria), Bacteriodetes, Chloroflexi and Actinobacteria, and most likely also in other phyla. Quantification of the microorganisms producing amyloid adhesins showed that they constituted at least 5-40% of all prokaryotes present in the biofilms, depending on the habitat. Particularly in drinking water biofilms, a high number of amyloid-positive bacteria were identified. Production of amyloids was confirmed by environmental isolates belonging to the Gammaproteobacteria, Bacteriodetes, Firmicutes and Actinobacteria. The new approach is a very useful tool for further culture-independent studies in mixed microbial communities, where the abundance and diversity of bacteria expressing amyloid adhesins seems much greater than hitherto anticipated. 相似文献
185.
186.
Thormann E Dreyer JK Simonsen AC Hansen PL Hansen S Holmskov U Mouritsen OG 《Biochemistry》2007,46(43):12231-12237
In order to investigate the dynamic strength of the interaction between lung surfactant protein D (SP-D) and different sugars, maltose, mannose, glucose, and galactose, we have used an atomic force microscope to monitor the interaction on a single molecule scale. The experiment is performed by measuring the rupture force when the SP-D-sugar bond is subjected to a continuously increasing force. Under these dynamic conditions, SP-D binds strongest to d-mannose and weakest to maltose and d-galactose. These results differ from equilibrium measurements wherein SP-D exhibits preference for maltose. On the basis of this finding, we propose that the binding of the disaccharide maltose to SP-D, which is energetically stronger than the binding of any of the monosacchrides, alters the structure of the binding site in a way that lowers the dynamic strength of the bond. We conclude that determining the strength of a protein-ligand bond under dynamic stress using an atomic force microscope is possibly more relevant for mimicking the actual nonequilibrium physiological situation in the lungs. 相似文献
187.
Marius Henriksen Tine Alkjaer Hans Lund Erik B Simonsen Thomas Graven-Nielsen Bente Danneskiold-Sams?e Henning Bliddal 《Journal of applied physiology》2007,103(1):132-139
Pain is a cardinal symptom in musculoskeletal diseases involving the knee joint, and aberrant movement patterns and motor control strategies are often present in these patients. However, the underlying neuromuscular mechanisms linking pain to movement and motor control are unclear. To investigate the functional significance of muscle pain on knee joint control during walking, three-dimensional gait analyses were performed before, during, and after experimentally induced muscle pain by means of intramuscular injections of hypertonic saline (5.8%) into vastus medialis (VM) muscle of 20 healthy subjects. Isotonic saline (0.9%) was used as control. Surface electromyography (EMG) recordings of VM, vastus lateralis (VL), biceps femoris, and semitendinosus muscles were synchronized with the gait analyses. During experimental muscle pain, the loading response phase peak knee extensor moments were attenuated, and EMG activity in the VM and VL muscles was reduced. Compressive forces, adduction moments, knee joint kinematics, and hamstring EMG activity were unaffected by pain. Interestingly, the observed changes persisted when the pain had vanished. The results demonstrate that muscle pain modulated the function of the quadriceps muscle, resulting in impaired knee joint control and joint instability during walking. The changes are similar to those observed in patients with knee pain. The loss of joint control during and after pain may leave the knee joint prone to injury and potentially participate in the chronicity of musculoskeletal problems, and it may have clinically important implications for rehabilitation and training of patients with knee pain of musculoskeletal origin. 相似文献
188.
Tollefsen S Hotta K Chen X Simonsen B Swaminathan K Mathews II Sollid LM Kim CY 《The Journal of biological chemistry》2012,287(17):13611-13619
MHC class II molecules are composed of one α-chain and one β-chain whose membrane distal interface forms the peptide binding groove. Most of the existing knowledge on MHC class II molecules comes from the cis-encoded variants where the α- and β-chain are encoded on the same chromosome. However, trans-encoded class II MHC molecules, where the α- and β-chain are encoded on opposite chromosomes, can also be expressed. We have studied the trans-encoded class II HLA molecule DQ2.3 (DQA1*03:01/DQB1*02:01) that has received particular attention as it may explain the increased risk of certain individuals to type 1 diabetes. We report the x-ray crystal structure of this HLA molecule complexed with a gluten epitope at 3.05 Å resolution. The gluten epitope, which is the only known HLA-DQ2.3-restricted epitope, is preferentially recognized in the context of the DQ2.3 molecule by T-cell clones of a DQ8/DQ2.5 heterozygous celiac disease patient. This preferential recognition can be explained by improved HLA binding as the epitope combines the peptide-binding motif of DQ2.5 (negative charge at P4) and DQ8 (negative charge at P1). The analysis of the structure of DQ2.3 together with all other available DQ crystal structures and sequences led us to categorize DQA1 and DQB1 genes into two groups where any α-chain and β-chain belonging to the same group are expected to form a stable heterodimer. 相似文献
189.
Lindmo K Simonsen A Brech A Finley K Rusten TE Stenmark H 《Experimental cell research》2006,312(11):2018-2027
Lysosomal degradation of cytoplasm by way of autophagy is essential for cellular amino acid homeostasis and for tissue remodeling. In insects such as Drosophila, autophagy is developmentally upregulated in the larval fat body prior to metamorphosis. Here, autophagy is induced by the hormone ecdysone through down-regulation of the autophagy-suppressive phosphoinositide 3-kinase (PI3K) signaling pathway. In yeast, Vps18 and other members of the HOPS complex have been found essential for autophagic degradation. In Drosophila, the Vps18 homologue Deep orange (Dor) has previously been shown to mediate fusion of multivesicular endosomes with lysosomes. A requirement of Dor for ecdysone-mediated chromosome puffing has also been reported. In the present report, we have tested the hypothesis that Dor may control programmed autophagy at the level of ecdysone signaling as well as by mediating autophagosome-to-lysosome fusion. We show that dor mutants are defective in programmed autophagy and provide evidence that autophagy is blocked at two levels. First, PI3K activity was not down-regulated correctly in dor larvae, which correlated with a decrease in ecdysone reporter activity. The down-regulation of PI3K activity was restored by feeding ecdysone to the mutant larvae. Second, neither exogenous ecdysone nor overexpression of PTEN, a silencer of PI3K signaling, restored fusion of autophagosomes with lysosomes in the fat body of dor mutants. These results indicate that Dor controls autophagy indirectly, via ecdysone signaling, as well as directly, via autolysosomal fusion. 相似文献
190.
Global Mortality Estimates for the 2009 Influenza Pandemic from the GLaMOR Project: A Modeling Study
Lone Simonsen Peter Spreeuwenberg Roger Lustig Robert J. Taylor Douglas M. Fleming Madelon Kroneman Maria D. Van Kerkhove Anthony W. Mounts W. John Paget the GLaMOR Collaborating Teams 《PLoS medicine》2013,10(11)