全文获取类型
收费全文 | 300篇 |
免费 | 35篇 |
专业分类
335篇 |
出版年
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 1篇 |
2019年 | 6篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2016年 | 10篇 |
2015年 | 20篇 |
2014年 | 29篇 |
2013年 | 28篇 |
2012年 | 29篇 |
2011年 | 34篇 |
2010年 | 15篇 |
2009年 | 16篇 |
2008年 | 19篇 |
2007年 | 11篇 |
2006年 | 22篇 |
2005年 | 15篇 |
2004年 | 12篇 |
2003年 | 15篇 |
2002年 | 11篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1982年 | 1篇 |
1974年 | 2篇 |
1971年 | 1篇 |
1969年 | 3篇 |
1966年 | 1篇 |
排序方式: 共有335条查询结果,搜索用时 15 毫秒
271.
Georg Jocher Vincent Grass Sarah K Tschirner Lydia Riepler Stephan Breimann Tuberk Kaya Madlen Oelsner M Sabri Hamad Laura I Hofmann Carl P Blobel Carsten B SchmidtWeber Ozgun Gokce Constanze A Jakwerth Jakob Trimpert Janine Kimpel Andreas Pichlmair Stefan F Lichtenthaler 《EMBO reports》2022,23(6)
The severe‐acute‐respiratory‐syndrome‐coronavirus‐2 (SARS‐CoV‐2) is the causative agent of COVID‐19, but host cell factors contributing to COVID‐19 pathogenesis remain only partly understood. We identify the host metalloprotease ADAM17 as a facilitator of SARS‐CoV‐2 cell entry and the metalloprotease ADAM10 as a host factor required for lung cell syncytia formation, a hallmark of COVID‐19 pathology. ADAM10 and ADAM17, which are broadly expressed in the human lung, cleave the SARS‐CoV‐2 spike protein (S) in vitro, indicating that ADAM10 and ADAM17 contribute to the priming of S, an essential step for viral entry and cell fusion. ADAM protease‐targeted inhibitors severely impair lung cell infection by the SARS‐CoV‐2 variants of concern alpha, beta, delta, and omicron and also reduce SARS‐CoV‐2 infection of primary human lung cells in a TMPRSS2 protease‐independent manner. Our study establishes ADAM10 and ADAM17 as host cell factors for viral entry and syncytia formation and defines both proteases as potential targets for antiviral drug development. 相似文献
272.
273.
Yvonne Teuschl Constanze Reim Barbara Meister Jacqueline Egger Wolf U. Blanckenhorn 《Ethology : formerly Zeitschrift fur Tierpsychologie》2010,116(11):1118-1126
The massive numbers of sperm males transfer during a single mating are physiologically costly and the amount of sperm that can be stored is limited. Therefore, males can perform only a finite number of successive copulations without loss of fertility, and males should allocate sperm prudently. We investigated sperm availability and depletion in male black scavenger flies, Sepsis cynipsea (Diptera: Sepsidae), asking whether males adjust copula duration according to nutrition, their sperm stores, their own and their partner’s body size, as predicted by theory. We created a gradient of sperm limitation by restricting dung (their protein resource as adults) and subjecting males to a varying number of copulations. While male fertility did not depend on access to fresh dung (contrary to females), it did decline after three copulations, and more so when males were small. Larger females tended to lay more unfertilized eggs after copulating with previously mated males. However, copula duration was not influenced by a male’s number of previous copulations, and therefore apparently not by his current sperm stores. Nevertheless, copula duration varied with male size, with small males copulating longer, and with female size, as copulations lasted longer with larger females, suggesting that males are investing more sperm in larger, more fecund females. While male copula adjustments to their own nutrition and body size may be simple (proximate) physiological responses, responses to female size indicate more strategic and sophisticated sperm‐allocation strategies than previously thought. 相似文献
274.
Brandstätter L Sokolova L Eicher T Seeger MA Briand C Cha HJ Cernescu M Bohnert J Kern WV Brutschy B Pos KM 《Biochimica et biophysica acta》2011,1808(9):2189-2196
The AcrA/AcrB/TolC complex is responsible for intrinsic multidrug resistance (MDR) in Escherichia coli. Together with the periplasmic adaptor protein AcrA and the outer membrane channel TolC, the inner membrane component AcrB forms an efflux complex that spans both the inner and outer membrane and bridges the periplasm of the Gram-negative cell. Within the entire tripartite complex, homotrimeric AcrB plays a central role in energy transduction and substrate selection. In vitro selected designed ankyrin repeat proteins (DARPin) that specifically bind to the periplasmic domain of AcrB were shown to ameliorate diffraction resolution of AcrB/DARPin protein co-crystals (G. Sennhauser, P. Amstutz, C. Briand, O. Storchenegger, M.G. Grutter, Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors, PLoS Biol 5 (2007) e7). Structural analysis by X-ray crystallography revealed that 2 DARPin molecules were bound to the trimeric AcrB wildtype protein in the crystal, whereas the V612F and G616N AcrB variant crystal structures show 3 DARPin molecules bound to the trimer. These specific stoichiometric differences were analyzed in solution via densitometry after microchannel electrophoresis, analytical ultracentrifugation and via laser-induced liquid bead ion desorption mass spectrometry (LILBID-MS). Using the latter technology, we investigated the gradual disassembly of the AcrB trimer and bound DARPin ligands in dependence on laser intensity in solution. At low laser intensity, the release of the detergent molecule micelle from the AcrB/DARPin complex was observed. By increasing laser intensity, dimeric and monomeric AcrB species with bound DARPin molecules were detected showing the high affinity binding of DARPin to monomeric AcrB species. High laser intensity LILBID MS experiments indicated a spectral shift of the monomeric AcrB peak of 3.1kDa, representing a low molecular weight ligand in all detergent-solubilized AcrB samples and in the AcrB crystal. The identity of this ligand was further investigated using phospholipid analysis of purified AcrB and AcrB variant samples, and indicated the presence of phosphatidylethanolamine and possibly cardiolipin, both constituents of the Escherichia coli membrane. 相似文献
275.
Ivanov I Di Venere A Horn T Scheerer P Nicolai E Stehling S Richter C Skrzypczak-Jankun E Mei G Maccarrone M Kühn H 《Biochimica et biophysica acta》2011,1811(12):1001-1010
12/15-Lipoxygenases (12/15-LOXs) have been implicated in inflammatory and hyperproliferative diseases but the structural biology of these enzymes is not well developed. Most LOXs constitute single polypeptide chain proteins that fold into a two-domain structure. In the crystal structure the two domains are tightly associated, but small angle X-ray scattering data and dynamic fluorescence studies suggested a high degree of structural flexibility involving movement of the N-terminal domain relative to catalytic subunit. When we inspected the interdomain interface we have found a limited number of side-chain contacts which are involved in interactions of these two structural subunits. One of such contact points involves tyrosine 98 of N-terminal domain. This aromatic amino acid is invariant in vertebrate LOXs regardless of overall sequence identity. To explore in more detail the role of aromatic interactions in interdomain association we have mutated Y98 to various residues and quantified the structural and functional consequences of these alterations. We have found that loss of an aromatic moiety at position 98 impaired the catalytic activity and membrane binding capacity of the mutant enzymes. Although CD and fluorescence emission spectra of wild-type and mutant enzyme species were indistinguishable, the mutation led to enlargement of the molecular shape of the enzyme as detected by analytic gel filtration and this structural alteration was shown to be associated with a loss of protein thermal stability. The possible role of tight interdomain association for the enzyme's structural performance is discussed. 相似文献
276.
277.
278.
279.
Heyden A Ionescu MC Romorini S Kracht B Ghiglieri V Calabresi P Seidenbecher C Angenstein F Gundelfinger ED 《Cell and tissue research》2011,346(1):11-26
Mice mutant for the presynaptic protein Bassoon develop epileptic seizures and an altered pattern of neuronal activity that
is accompanied by abnormal enlargement of several brain structures, with the strongest size increase in hippocampus and cortex.
Using manganese-enhanced magnetic resonance imaging, an abnormal brain enlargement was found, which is first detected in the
hippocampus 1 month after birth and amounts to an almost 40% size increase of this structure after 3 months. Stereological
quantification of cell numbers revealed that enlargement of the dentate gyrus and the hippocampus proper is associated with
larger numbers of principal neurons and of astrocytes. In search for the underlying mechanisms, an approximately 3-fold higher
proportion of proliferation and survival of new-born cells in the dentate gyrus was found to go hand in hand with similarly
larger numbers of doublecortin-positive cells and reduced numbers of apoptotic cells in the dentate gyrus and the hippocampus
proper. Enlargement of the hippocampus and of other forebrain structures was accompanied by increased levels of brain-derived
neurotrophic factor (BDNF). These data show that hippocampal overgrowth in Bassoon-mutant mice arises from a dysregulation
of neurogenesis and apoptosis that might be associated with unbalanced BDNF levels. 相似文献
280.
Synaptopathies: synaptic dysfunction in neurological disorders – A review from students to students
下载免费PDF全文
![点击此处可从《Journal of neurochemistry》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Katarzyna Lepeta Mychael V. Lourenco Barbara C. Schweitzer Pamela V. Martino Adami Priyanjalee Banerjee Silvina Catuara‐Solarz Mario de La Fuente Revenga Alain Marc Guillem Mouna Haidar Omamuyovwi M. Ijomone Bettina Nadorp Lin Qi Nirma D. Perera Louise K. Refsgaard Kimberley M. Reid Mariam Sabbar Arghyadip Sahoo Natascha Schaefer Rebecca K. Sheean Anna Suska Rajkumar Verma Cinzia Vicidomini Dean Wright Xing‐Ding Zhang Constanze Seidenbecher 《Journal of neurochemistry》2016,138(6):785-805