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排序方式: 共有241条查询结果,搜索用时 15 毫秒
11.
Bella S. Galil Ferdinando Boero Marnie L. Campbell James T. Carlton Elizabeth Cook Simonetta Fraschetti Stephan Gollasch Chad L. Hewitt Anders Jelmert Enrique Macpherson Agnese Marchini Cynthia McKenzie Dan Minchin Anna Occhipinti-Ambrogi Henn Ojaveer Sergej Olenin Stefano Piraino Gregory M. Ruiz 《Biological invasions》2015,17(4):973-976
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Benito J Shi Y Szymanska B Carol H Boehm I Lu H Konoplev S Fang W Zweidler-McKay PA Campana D Borthakur G Bueso-Ramos C Shpall E Thomas DA Jordan CT Kantarjian H Wilson WR Lock R Andreeff M Konopleva M 《PloS one》2011,6(8):e23108
Recent studies indicate that interactions between leukemia cells and the bone marrow (BM) microenvironment promote leukemia cell survival and confer resistance to anti-leukemic drugs. There is evidence that BM microenvironment contains hypoxic areas that confer survival advantage to hematopoietic cells. In the present study we investigated whether hypoxia in leukemic BM contributes to the protective role of the BM microenvironment. We observed a marked expansion of hypoxic BM areas in immunodeficient mice engrafted with acute lymphoblastic leukemia (ALL) cells. Consistent with this finding, we found that hypoxia promotes chemoresistance in various ALL derived cell lines. These findings suggest to employ hypoxia-activated prodrugs to eliminate leukemia cells within hypoxic niches. Using several xenograft models, we demonstrated that administration of the hypoxia-activated dinitrobenzamide mustard, PR-104 prolonged survival and decreased leukemia burden of immune-deficient mice injected with primary acute lymphoblastic leukemia cells. Together, these findings strongly suggest that targeting hypoxia in leukemic BM is feasible and may significantly improve leukemia therapy. 相似文献
15.
Coles M Djuranovic S Söding J Frickey T Koretke K Truffault V Martin J Lupas AN 《Structure (London, England : 1993)》2005,13(6):919-928
AbrB is a key transition-state regulator of Bacillus subtilis. Based on the conservation of a betaalphabeta structural unit, we proposed a beta barrel fold for its DNA binding domain, similar to, but topologically distinct from, double-psi beta barrels. However, the NMR structure revealed a novel fold, the "looped-hinge helix." To understand this discrepancy, we undertook a bioinformatics study of AbrB and its homologs; these form a large superfamily, which includes SpoVT, PrlF, MraZ, addiction module antidotes (PemI, MazE), plasmid maintenance proteins (VagC, VapB), and archaeal PhoU homologs. MazE and MraZ form swapped-hairpin beta barrels. We therefore reexamined the fold of AbrB by NMR spectroscopy and found that it also forms a swapped-hairpin barrel. The conservation of the core betaalphabeta element supports a common evolutionary origin for swapped-hairpin and double-psi barrels, which we group into a higher-order class, the cradle-loop barrels, based on the peculiar shape of their ligand binding site. 相似文献
16.
The positioning and dynamics of organelles depend on membrane-cytoskeleton interactions. Mitochondria relocate along microtubules (MT), but it is not clear whether MT have direct effects on mitochondrial function. Using two-photon microscopy and the mitochondrial fluorescent dyes rhodamine 123 and Rhod-2, we showed that Taxol and nocodazole, which correspondingly stabilize and disrupt MT, decreased potential and Ca(2+) in the mitochondria of brain stem pre-Botzinger complex neurons. Without changing basal cytoplasmic Ca(2+) ([Ca(2+)](i)), Taxol promoted the generation of [Ca(2+)](i) spikes in dendrites. These spikes were abolished after blockade of Ca(2+) influx and after depletion of internal Ca(2+) stores, indicating the involvement of Ca(2+)-induced Ca(2+) release. Nocodazole decreased mitochondrial potential and [Ca(2+)](m) and produced a long lasting increase in [Ca(2+)](i). MT-acting drugs depolarized single immobilized mitochondria and released previously stored Ca(2+). All of these effects were inhibited by pretreatment with blockers of mitochondrial permeability transition pore (mPTP), cyclosporin A, and 2-aminoethoxydiphenyl borate. Induction of mPTP by Taxol and nocodazole was confirmed by using a calcein/Co(2+) imaging technique. Electron and optical microscopy revealed tubulin bound to mitochondria. Mitochondria, MT, and endoplasmic reticulum (ER) showed strong co-localization, the degree of which decreased after MT were disrupted. We propose that changes in the structure of MT by Taxol and nocodazole promote the induction of mPTP. Subsequent Ca(2+) efflux stimulates the Ca(2+) release from the ER that drives spontaneous [Ca(2+)](i) transients. Thus, close positioning of mitochondria to the ER as determined by MT can be essential for the local [Ca](i) signaling in neurons. 相似文献
17.
Katarina Jewgenow Frank Goeritz Katrin Neubauer Joerns Fickel Sergej V. Naidenko 《European Journal of Wildlife Research》2006,52(1):34-38
This study characterizes the reproductive activity of male European lynx kept in Central Russia. Four captive adult males
were subjected to an electroejaculation prior to (November), during (March) and after (June) the breeding season. Concentration,
motility and morphological integrity of spermatozoa as well as testis diameter and testosterone levels in serum were evaluated.
Additionally, fecal samples were collected for 2 years to determine the fecal testosterone secretion. Testis sizes and serum
testosterone concentrations were characterized by little changes with highest levels in March (2.98 mm3; 1.96 ng/ml testosterone) and lowest in June (2.34 mm3; 0.75 ng/ml testosterone). In faeces, the highest testosterone concentrations were measured in February followed by a second
increase in May. The volume of ejaculates and percentages of motile and intact spermatozoa reached the maxima in March. By
performing two-male mating experiments, we could prove multiple paternity within three litters. Paternity analysis of litter
also revealed that 26 of 31 cubs (84%) were sired from the same male, independently from being the first or second mating
partner of the respective female. This particular male showed the most developed and activated reproductive tract and also
had the best semen quality, which seems to be important for sperm competition. 相似文献
18.
Darius Daunys Petras Zemlys Sergej Olenin Anastasija Zaiko Christian Ferrarin 《Helgoland Marine Research》2006,60(2):113-120
The role of the zebra mussel Dreissena polymorpha in redistribution of total particulate material (TPM) between the water column and bottom sediment was estimated using the TPM budget for a mussel bed in the Curonian lagoon, the Baltic Sea. Seasonal clearance rates were derived from the TPM budget assuming two resuspension scenarios: no resuspension and full resuspension of biodeposits. Estimated clearance rates for both scenarios were compared with the rates calculated from the population clearance rate model. Seasonal clearance rates estimated using the population model (1.1 and 11.8 l g−1 SFDW day−1) fitted well into the interval of seasonal clearance rates calculated from TPM budgets assuming no resuspension of biodeposits (3.2 and 21.4 l g SFDW−1 day−1). In the scenario with biodeposits resuspension clearance rates were much higher (57.4 and 148.9 g SFDW−1 day−1). The ratio of clearance to residence time was highly dependent on the fate of biodeposits. Therefore its use in interpretation of the species impact on TPM was limited. An alternative measure based on the ratio of the amount of TPM biodeposited to TPM transported into the bed was used. It was found that zebra mussels are able to deposit between 10 and 30% of the incoming TPM, and the amount of biodeposited material was correlated with water residence time. Results indicate that the impact of zebra mussels on TPM in the lagoon is small relative to the high transport rates of TPM over the bed. However, annual biosedimentation rate (~590 g m−2) in the mussel bed was higher than physical deposition rate (~380 g m−2) in accumulation areas devoid of large suspension feeders. We suggest that a local impact due to enhanced availability of organic material to other trophic groups of associated benthic organisms may be more significant than effects on TPM pathways at an ecosystem scale. 相似文献
19.
A protein dynamics study of photosystem II: the effects of protein conformation on reaction center function 总被引:2,自引:0,他引:2
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Molecular dynamics simulations have been performed to study photosystem II structure and function. Structural information obtained from simulations was combined with ab initio computations of chromophore excited states. In contrast to calculations based on the x-ray structure, the molecular-dynamics-based calculations accurately predicted the experimental absorbance spectrum. In addition, our calculations correctly assigned the energy levels of reaction-center (RC) chromophores, as well as the lowest-energy antenna chlorophyll. The primary and secondary quinone electron acceptors, QA and QB, exhibited independent changes in position over the duration of the simulation. QB fluctuated between two binding sites similar to the proximal and distal sites previously observed in light- and dark-adapted RC from purple bacteria. Kinetic models were used to characterize the relative influence of chromophore geometry, site energies, and electron transport rates on RC efficiency. The fluctuating energy levels of antenna chromophores had a larger impact on quantum yield than did their relative positions. Variations in electron transport rates had the most significant effect and were sufficient to explain the experimentally observed multi-component decay of excitation in photosystem II. The implications of our results are discussed in the context of competing evolutionary selection pressures for RC structure and function. 相似文献
20.
Susanne Roth Mobarak Abu Mraheil Winfried Barchet Jan Böttcher Torsten Hain Sergej Geiger Yoshihiro Hayakawa Jörg H Fritz Filiz Civril Karl‐Peter Hopfner Christian Kurts Jürgen Ruland Gunther Hartmann Trinad Chakraborty Percy A Knolle 《The EMBO journal》2012,31(21):4153-4164
Immunity against infection with Listeria monocytogenes is not achieved from innate immune stimulation by contact with killed but requires viable Listeria gaining access to the cytosol of infected cells. It has remained ill‐defined how such immune sensing of live Listeria occurs. Here, we report that efficient cytosolic immune sensing requires access of nucleic acids derived from live Listeria to the cytoplasm of infected cells. We found that Listeria released nucleic acids and that such secreted bacterial RNA/DNA was recognized by the cytosolic sensors RIG‐I, MDA5 and STING thereby triggering interferon β production. Secreted Listeria nucleic acids also caused RIG‐I‐dependent IL‐1β‐production and inflammasome activation. The signalling molecule CARD9 contributed to IL‐1β production in response to secreted nucleic acids. In conclusion, cytosolic recognition of secreted bacterial nucleic acids by RIG‐I provides a mechanistic explanation for efficient induction of immunity by live bacteria. 相似文献