全文获取类型
收费全文 | 468篇 |
免费 | 57篇 |
出版年
2021年 | 4篇 |
2020年 | 5篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 12篇 |
2014年 | 11篇 |
2013年 | 40篇 |
2012年 | 27篇 |
2011年 | 13篇 |
2010年 | 15篇 |
2009年 | 15篇 |
2008年 | 17篇 |
2007年 | 19篇 |
2006年 | 20篇 |
2005年 | 21篇 |
2004年 | 19篇 |
2003年 | 21篇 |
2002年 | 8篇 |
2001年 | 18篇 |
2000年 | 15篇 |
1999年 | 12篇 |
1998年 | 8篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 8篇 |
1992年 | 15篇 |
1991年 | 11篇 |
1990年 | 6篇 |
1989年 | 10篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1986年 | 8篇 |
1985年 | 4篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 9篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1975年 | 3篇 |
1972年 | 3篇 |
1970年 | 3篇 |
1969年 | 4篇 |
1965年 | 3篇 |
1928年 | 3篇 |
1927年 | 4篇 |
1926年 | 2篇 |
1925年 | 4篇 |
排序方式: 共有525条查询结果,搜索用时 31 毫秒
81.
Patrick Martin Enrique Martinez-Ansemil Adrian Pinder Tarmo Timm Mark J. Wetzel 《Hydrobiologia》2008,606(1):117-127
One of the predicted consequences of climate change is an increase in the occurrence of extreme rainfall and a subsequent
increase in frequency of high flow events in rivers. High flow events have the potential to impact estuarine communities like
mussel assemblages due to decreased salinity and/or the transport of sediments, organic matter and nutrients from the terrestrial
environment to the estuary. The impact of two high flow events was investigated using mussels located within the Conwy estuary,
North Wales, using the ‘Beyond BACI’ approach. Three study sites were chosen, the potentially impacted site (Conwy) and two
control sites located outside the estuary. Sampling took place over 18 months with samples being collected before and after
each event. On each sampling occasion, the following data were collected: the total haemocyte count (THC) and condition index
(CI) of the mussels and the diversity (Hloge) of their associated macrofauna. A significant effect of the first event (22nd October 2004) was found on the CI of the Conwy
mussels, whereas a significant effect of the second event (10th October 2005) was found on mussel THC. No effect of either
event was found on the diversity of the associated fauna. The results of this study suggest that any increase in the number
or intensity of heavy precipitation or high flow events have potential implications for the health and resilience of estuarine
mussel populations.
Guest editors: J. Davenport, G. Burnell, T. Cross, M. Emmerson, R. McAllen, R. Ramsay & E. Rogan
Challenges to Marine Ecosystems 相似文献
82.
Patrick Winterhagen Cornelia Dubois Melanie Sinn Thierry Wetzel Götz M. Reustle 《Plant Physiology and Biochemistry》2009,47(8):739-742
RNA interference (RNAi) was established in Nicotiana benthamiana plants by introducing constructs containing a defective interfering (DI) sequence from Tomato bushy stunt virus (TBSV) in combination with a conserved sense-sequence from the target Grapevine fanleaf virus (GFLV). Silencing in plants was confirmed by Agrobacterium-mediated infiltration of a GFP-sensor containing the GFLV-derived target sequence. The transgene-induced RNAi led to silencing of the GFP-sensor and GFP fluorescence was absent post-infiltration. In plants without GFP fluorescence after infiltration with the GFP-sensor, siRNA specific to GFP and the target virus sequence could not be detected. In contrast, infiltrated leaves of wild type and transgenic plants showing GFP fluorescence after infiltration revealed accumulation of siRNA specific to the sequence of the sensor. Silencing could be inhibited by co-infiltration using a p19 silencing suppressor construct together with the GFP-sensor, which always resulted in bright GFP fluorescence. In parallel, virus resistance of transgenic Nicotiana benthamiana was investigated via challenge inoculation with GFLV. Our results indicate that efficient RNAi in transgenic plants does not necessarily lead to a detectable accumulation of siRNA. 相似文献
83.
Paul R. Wetzel Arnold G. van der Valk Susan Newman Carlos A. Coronado Tiffany G. Troxler-Gann Daniel L. Childers William H. Orem Fred H. Sklar 《Plant Ecology》2009,200(1):83-90
The biologically mediated transfer of nutrients from one part of a landscape to another may create nutrient gradients or subsidize
the productivity at specific locations. If limited, this focused redistribution of the nutrient may create non-random landscape
patterns that are unrelated to underlying environmental gradients. The Florida Everglades, USA, is a large freshwater wetland
that is patterned with tree islands, elevated areas that support woody vegetation. A survey of 12 tree islands found total
soil phosphorus levels 3–114 times greater on the island head than the surrounding marsh, indicating that the Florida Everglades
is not a homogeneous oligotrophic system. It was estimated that historically 67% of the phosphorus entering the central Everglades
was sequestered on tree islands, which are ~3.8% of the total land area. This internal redistribution of phosphorus onto tree
islands due to the establishment of trees may be one reason that marshes have remained oligotrophic and may explain the spatial
differentiation of the patterned Everglades landscape. 相似文献
84.
85.
Bhattacharyya A Thakur AK Chellgren VM Thiagarajan G Williams AD Chellgren BW Creamer TP Wetzel R 《Journal of molecular biology》2006,355(3):524-535
There are nine known expanded CAG repeat neurological diseases, including Huntington's disease (HD), each involving the repeat expansion of polyglutamine (polyGln) in a different protein. Similar conditions can be induced in animal models by expression of the polyGln sequence alone or in other protein contexts. Besides the polyGln sequence, the cellular context of the disease protein, and the sequence context of the polyGln within the disease protein, are both likely to contribute to polyGln physical behavior and to pathology. In HD, the N-terminal, exon-1 segment of the protein huntingtin contains the polyGln sequence immediately followed by an oligoproline region. We show here that introduction of a P10 sequence C-terminal to polyGln in synthetic peptides decreases both the rate of formation and the apparent stability of the amyloid-like aggregates associated with this family of diseases. The sequence can be trimmed to P6 without altering the suppression, but a P3 sequence is ineffective. Spacers up to at least three amino acid residues in length can be inserted between polyGln and P10 without altering this effect. There is no suppression, however, when the P10 sequence is either placed on the N-terminal side of polyGln or attached to polyGln via a side-chain tether. The nucleation mechanism of a Q40 sequence is unchanged upon addition of a P10 C-terminal extension, yielding a critical nucleus of one. The effects of oligoPro length and structural context on polyGln aggregation are correlated strongly with alterations in the circular dichroism spectra of the monomeric peptides. For example, the P10 sequence eliminates the small amount of alpha helical content otherwise exhibited by the Q40 sequence. The P10 sequence may suppress aggregation by stabilizing an aggregation-incompetent conformation of the monomer. The effect is transportable: a P10 sequence fixed to the C terminus of the sequence Abeta similarly modulates amyloid fibril formation. 相似文献
86.
Alfalah M Krahn MP Wetzel G von Hörsten S Wolke C Hooper N Kalinski T Krueger S Naim HY Lendeckel U 《The Journal of biological chemistry》2006,281(17):11894-11900
Human aminopeptidase N (APN) is used as a routine marker for myelomonocytic cells in hematopoietic malignant disorders. Its gene and surface expressions are increased in cases of malignant transformation, inflammation, or T cell activation, whereas normal B and resting T cells lack detectable APN protein expression. In this study we elucidated the intracellular distribution, expression pattern, and enzymatic activity of a naturally occurring mutation in the coding region of the APN gene. At physiological temperatures the mutant protein is enzymatically inactive, persists as a mannose-rich polypeptide in the endoplasmic reticulum, and is ultimately degraded by an endoplasmic reticulum-associated degradation pathway. It shows in part the distinct behavior of a temperature-sensitive mutant with a permissive temperature of 32 degrees C, leading to correct sorting of the Golgi compartment accompanied by the acquisition of proper glycosylation but without reaching the cell-surface membrane and without regaining its enzymatic activity. Because the patient bearing this mutation suffered from leukemia, possible links to the pathogenesis of leukemia are discussed. 相似文献
87.
We describe here the use of cysteine substitution mutants in the Alzheimer disease amyloid plaque peptide Abeta-(1-40) to probe amyloid fibril structure and stabilization. In one approach, amyloid fibrils were grown from Cys mutant peptides under reducing conditions and then challenged with an alkylating agent to probe solvent accessibility of different residues in the fibril. In another approach, monomeric Cys mutants, either in the thiol form or modified with iodoacetic acid or methyl iodide, were grown into amyloid fibrils, and the equilibrium position at the end of the amyloid formation reaction was quantified by determining the concentration of monomeric Abeta. The DeltaG values of fibril elongation obtained were then compared in order to provide information on the environment of each residue side chain in the fibril. In general, Cys residues in the N and C termini of Abeta-(1-40) were not only accessible to alkylation in the fibril state but also, when modified in the monomeric state, did not greatly impact fibril stability; these observations were consistent with previous indications that these portions of the peptide are not part of the amyloid core. In contrast, residues 16-19 and 31-34 were not only uniformly inaccessible to alkylation in the fibril state, but their modification with the negatively charged carboxymethyl group in monomeric Abeta also destabilized fibril elongation, confirming other data showing that these segments are likely packed into a hydrophobic amyloid core. Residues 20, 30, and 35, flanking these implicated beta-sandwich regions, are accessible to alkylation in the fibril indicating a location in solvent exposed structure. 相似文献
88.
Hallerdei J Scheibe RJ Parkkila S Waheed A Sly WS Gros G Wetzel P Endeward V 《PloS one》2010,5(12):e15137
We have studied lactic acid transport in the fast mouse extensor digitorum longus muscles (EDL) by intracellular and cell surface pH microelectrodes. The role of membrane-bound carbonic anhydrases (CA) of EDL in lactic acid transport was investigated by measuring lactate flux in muscles from wildtype, CAIV-, CAIX- and CAXIV-single ko, CAIV-CAXIV double ko and CAIV-CAIX-CAXIV-triple ko mice. This was complemented by immunocytochemical studies of the subcellular localization of CAIV, CAIX and CAXIV in mouse EDL. We find that CAXIV and CAIX single ko EDL exhibit markedly but not maximally reduced lactate fluxes, whereas triple ko and double ko EDL show maximal or near-maximal inhibition of CA-dependent lactate flux. Interpretation of the flux measurements in the light of the immunocytochemical results leads to the following conclusions. CAXIV, which is homogeneously distributed across the surface membrane of EDL fibers, facilitates lactic acid transport across this membrane. CAIX, which is associated only with T tubular membranes, facilitates lactic acid transport across the T tubule membrane. The removal of lactic acid from the lumen of T tubuli towards the interstitial space involves a CO2-HCO3- diffusional shuttle that is maintained cooperatively by CAIX within the T tubule and, besides CAXIV, by the CAIV, which is strategically located at the opening of the T tubules. The data suggest that about half the CA-dependent muscular lactate flux occurs across the surface membrane, while the other half occurs across the membranes of the T tubuli. 相似文献
89.
Gisselmann G Warnstedt M Gamerschlag B Bormann A Marx T Neuhaus EM Stoertkuhl K Wetzel CH Hatt H 《Insect biochemistry and molecular biology》2003,33(11):1123-1134
Recently, a novel class of genes coding for Ih-channels has been identified in several vertebrates and invertebrates. We isolated a cDNA (AMIH) encoding a putative member of these ion channels from Apis mellifera heads by means of polymerase chain reaction and homology screening. High similarity (88% identical amino acids) to the putative Drosophila melanogaster Ih-channel suggests that the Apis cDNA codes for a hyperpolarization-activated and cyclic nucleotide-gated channel. Functional expression of recombinant AMIH in HEK293 cells gave unitary currents that were preferentially selective for potassium over sodium ions and were activated by hyperpolarizing voltage steps. Cyclic nucleotides shifted the voltage activation curve to more positive membrane potentials. The current kinetics, activation by hyperpolarizing voltage steps and modulatory influence of cyclic nucleotides properties closely resemble those of mammalian Ih-channels. RT-PCR analysis showed pronounced mRNA expression in the antennae, head and body of Apis mellifera. Investigation of hyperpolarization-activated currents in olfactory receptor neurons (ORNs) in a primary cell culture of Apis mellifera antennal cells revealed activation properties similar to the heterologously expressed Ih-channel. By in-situ hybridization and immunohistochemistry, expression of AMIH was seen in olfactory receptor neurons of the bee antennae. We conclude that AMIH is the ion channel responsible for the hyperpolarization-activated currents in olfactory receptor neurons of bee. 相似文献
90.