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Ilona Schonn Jana Hennesen Dorothee C. Dartsch 《Apoptosis : an international journal on programmed cell death》2010,15(2):162-172
The topoisomerase IIα inhibitor etoposide is a ‘broad spectrum’ anticancer agent and a potent inducer of DNA double strand
breaks. DNA damage response of mammalian cells usually involves cell cycle arrest and DNA repair or, if unsuccessful, cell
death. We investigated these processes in the human colon cancer cell line HT-29 treated with three different etoposide regimens
mimicking clinically relevant plasma concentrations of cancer patients. Each involved a period of drug-free incubation following
etoposide exposure to imitate the decline of plasma levels between the cycles of chemotherapy. We found a massive induction
of double strand breaks that were rapidly and nearly completely fixed long before the majority of cells underwent apoptosis
or necrosis. An even greater percentage of cells lost clonogenicity. The occurrence of double strand breaks was accompanied
by a decrease in the levels of Ku70, Ku86 and DNA-PKcs as well as an increase in the level of Rad51 protein. Twenty-four hours after the first contact with etoposide we found a
pronounced G2/M arrest, regardless of the duration of drug exposure, the level of double strand breaks and the extent of their repair.
During the subsequent drug-free incubation period, the loss of clonogenicity correlated well with the preceding G2/M arrest as well as with the amount of cell death found several days after exposure. However, it correlated neither with
early apoptosis or necrosis nor with any of the other investigated parameters. These results suggest that the G2/M arrest is an important determinant in the cytostatic action of etoposide and that the removal of DNA double strand breaks
is not sufficient to ensure cell survival. 相似文献
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Benjamin Zienicke Isabel Molina René Glenz Patrick Singer Dorothee Ehmer Francisco Velazquez Escobar Peter Hildebrandt Rolf Diller Tilman Lamparter 《The Journal of biological chemistry》2013,288(44):31738-31751
Phytochromes are widely distributed photoreceptors with a bilin chromophore that undergo a typical reversible photoconversion between the two spectrally different forms, Pr and Pfr. The phytochrome Agp2 from Agrobacterium tumefaciens belongs to the group of bathy phytochromes that have a Pfr ground state as a result of the Pr to Pfr dark conversion. Agp2 has untypical spectral properties in the Pr form reminiscent of a deprotonated chromophore as confirmed by resonance Raman spectroscopy. UV/visible absorption spectroscopy showed that the pKa is >11 in the Pfr form and ∼7.6 in the Pr form. Unlike other phytochromes, photoconversion thus results in a pKa shift of more than 3 units. The Pr/Pfr ratio after saturating irradiation with monochromatic light is strongly pH-dependent. This is partially due to a back-reaction of the deprotonated Pr chromophore at pH 9 after photoexcitation as found by flash photolysis. The chromophore protonation and dark conversion were affected by domain swapping and site-directed mutagenesis. A replacement of the PAS or GAF domain by the respective domain of the prototypical phytochrome Agp1 resulted in a protonated Pr chromophore; the GAF domain replacement afforded an inversion of the dark conversion. A reversion was also obtained with the triple mutant N12S/Q190L/H248Q, whereas each single point mutant is characterized by decelerated Pr to Pfr dark conversion. 相似文献
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Spatial heterogeneity in species composition constrains plant community responses to herbivory and fertilisation
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![点击此处可从《Ecology letters》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Dorothee Hodapp Elizabeth T. Borer W. Stanley Harpole Eric M. Lind Eric W. Seabloom Peter B. Adler Juan Alberti Carlos A. Arnillas Jonathan D. Bakker Lori Biederman Marc Cadotte Elsa E. Cleland Scott Collins Philip A. Fay Jennifer Firn Nicole Hagenah Yann Hautier Oscar Iribarne Johannes M. H. Knops Rebecca L. McCulley Andrew MacDougall Joslin L. Moore John W. Morgan Brent Mortensen Kimberly J. La Pierre Anita C. Risch Martin Schütz Pablo Peri Carly J. Stevens Justin Wright Helmut Hillebrand 《Ecology letters》2018,21(9):1364-1371
Environmental change can result in substantial shifts in community composition. The associated immigration and extinction events are likely constrained by the spatial distribution of species. Still, studies on environmental change typically quantify biotic responses at single spatial (time series within a single plot) or temporal (spatial beta diversity at single time points) scales, ignoring their potential interdependence. Here, we use data from a global network of grassland experiments to determine how turnover responses to two major forms of environmental change – fertilisation and herbivore loss – are affected by species pool size and spatial compositional heterogeneity. Fertilisation led to higher rates of local extinction, whereas turnover in herbivore exclusion plots was driven by species replacement. Overall, sites with more spatially heterogeneous composition showed significantly higher rates of annual turnover, independent of species pool size and treatment. Taking into account spatial biodiversity aspects will therefore improve our understanding of consequences of global and anthropogenic change on community dynamics. 相似文献
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Nimodipine confers clinical improvement in two models of experimental autoimmune encephalomyelitis
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![点击此处可从《Journal of neurochemistry》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Jens Ingwersen Lorenzo De Santi Britta Wingerath Jonas Graf Barbara Koop Reiner Schneider Christina Hecker Friederike Schröter Mary Bayer Anna Dorothee Engelke Michael Dietrich Philipp Albrecht Hans‐Peter Hartung Pasquale Annunziata Orhan Aktas Tim Prozorovski 《Journal of neurochemistry》2018,146(1):86-98
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