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991.
992.
993.
Hypericin, an extract from St John''s Wort (Hypericum perforatum L.), is a promising photosensitizer in the context of clinical photodynamic therapy due to its excellent photosensitizing properties and tumoritropic characteristics. Hypericin-PDT induced cytotoxicity elicits tumor cell death by various mechanisms including apoptosis, necrosis and autophagy-related cell death. However, limited reports on the efficacy of this photomedicine for the treatment of melanoma have been published. Melanoma is a highly aggressive tumor due to its metastasizing potential and resistance to conventional cancer therapies. The aim of this study was to investigate the response mechanisms of melanoma cells to hypericin-PDT in an in vitro tissue culture model. Hypericin was taken up by all melanoma cells and partially co-localized to the endoplasmic reticulum, mitochondria, lysosomes and melanosomes, but not the nucleus. Light activation of hypericin induced a rapid, extensive modification of the tubular mitochondrial network into a beaded appearance, loss of structural details of the endoplasmic reticulum and concomitant loss of hypericin co-localization. Surprisingly the opposite was found for lysosomal-related organelles, suggesting that the melanoma cells may be using these intracellular organelles for hypericin-PDT resistance. In line with this speculation we found an increase in cellular granularity, suggesting an increase in pigmentation levels in response to hypericin-PDT. Pigmentation in melanoma is related to a melanocyte-specific organelle, the melanosome, which has recently been implicated in drug trapping, chemotherapy and hypericin-PDT resistance. However, hypericin-PDT was effective in killing both unpigmented (A375 and 501mel) and pigmented (UCT Mel-1) melanoma cells by specific mechanisms involving the externalization of phosphatidylserines, cell shrinkage and loss of cell membrane integrity. In addition, this treatment resulted in extrinsic (A375) and intrinsic (UCT Mel-1) caspase-dependent apoptotic modes of cell death, as well as a caspase-independent apoptotic mode that did not involve apoptosis-inducing factor (501 mel). Further research is needed to shed more light on these mechanisms. 相似文献
994.
Madalina E. Tivarus Britta Pester Christoph Schmidt Thomas Lehmann Tong Zhu Jianhui Zhong Lutz Leistritz Giovanni Schifitto 《PloS one》2015,10(10)
Lithium therapy has been shown to affect imaging measures of brain function and microstructure in human immunodeficiency virus (HIV)-infected subjects with cognitive impairment. The aim of this proof-of-concept study was to explore whether changes in brain microstructure also entail changes in functional connectivity. Functional MRI data of seven cognitively impaired HIV infected individuals enrolled in an open-label lithium study were included in the connectivity analysis. Seven regions of interest (ROI) were defined based on previously observed lithium induced microstructural changes measured by Diffusion Tensor Imaging. Generalized partial directed coherence (gPDC), based on time-variant multivariate autoregressive models, was used to quantify the degree of connectivity between the selected ROIs. Statistical analyses using a linear mixed model showed significant differences in the average node strength between pre and post lithium therapy conditions. Specifically, we found that lithium treatment in this population induced changes suggestive of increased strength in functional connectivity. Therefore, by exploiting the information about the strength of functional interactions provided by gPDC we can quantify the connectivity changes observed in relation to a given intervention. Furthermore, in conditions where the intervention is associated with clinical changes, we suggest that this methodology could enable an interpretation of such changes in the context of disease or treatment induced modulations in functional networks. 相似文献
995.
Correlating plant litter decay rates with initial tissue traits (e.g. C, N contents) is common practice, but in woody litter, predictive relationships are often weak. Variability in predicting wood decomposition is partially due to territorial competition among fungal decomposers that, in turn, have a range of nutritional strategies (rot types) and consequences on residues. Given this biotic influence, researchers are increasingly using culture-independent tools in an attempt to link variability more directly to decomposer groups. Our goal was to complement these tools by using certain wood modifications as ‘signatures’ that provide more functional information about decomposer dominance than density loss. Specifically, we used dilute alkali solubility (DAS; higher for brown rot) and lignin:density loss (L:D; higher for white rot) to infer rot type (binary) and fungal nutritional mode (gradient), respectively. We first determined strength of pattern among 29 fungi of known rot type by correlating DAS and L:D with mass loss in birch and pine. Having shown robust relationships for both techniques above a density loss threshold, we then demonstrated and resolved two issues relevant to species consortia and field trials, 1) spatial patchiness creating gravimetric bias (density bias), and 2) brown rot imprints prior or subsequent to white rot replacement (legacy effects). Finally, we field-tested our methods in a New Zealand Pinus radiata plantation in a paired-plot comparison. Overall, results validate these low-cost techniques that measure the collective histories of decomposer dominance in wood. The L:D measure also showed clear potential in classifying ‘rot type’ along a spectrum rather than as a traditional binary type (brown versus white rot), as it places the nutritional strategies of wood-degrading fungi on a scale (L:D=0-5, in this case). These information-rich measures of consequence can provide insight into their biological causes, strengthening the links between traits, structure, and function during wood decomposition. 相似文献
996.
Elzbieta Stepula Matthias Knig Xin‐Ping Wang Janina Levermann Tobias Schimming Sabine Kasimir‐Bauer Bastian Schilling Sebastian Schlücker 《Journal of biophotonics》2020,13(3)
Programmed cell death‐ligand 1 (PD‐L1) is an important predictive biomarker. The detection of PD‐L1 can be crucial for patients with advanced cancer where the use of immunotherapy is considered. Here, we demonstrate the use of immuno‐SERS microscopy (iSERS) for localizing PD‐L1 on single cancer SkBr‐3 cells. A central advantage of iSERS is that the disturbing autofluorescence from cells and tissues can be efficiently minimized by red to near‐infrared laser excitation. In this study we employed Au/Au core/satellite nanoparticles as SERS nanotags because of their remarkable signal brightness and colloidal stability upon red laser excitation. False‐color iSERS images of the positive and negative controls clearly reveal the specific localization of PD‐L1 with SERS nanotag‐labeled antibodies. 相似文献
997.
Puneet Garg Rakesh Verma Leslie Cook Abdul Soofi Madhusudan Venkatareddy Britta George Kensaku Mizuno Christine Gurniak Walter Witke Lawrence B. Holzman 《The Journal of biological chemistry》2010,285(29):22676-22688
Actin dynamics determines podocyte morphology during development and in response to podocyte injury and might be necessary for maintaining normal podocyte morphology. Because podocyte intercellular junction receptor Nephrin plays a role in regulating actin dynamics, and given the described role of cofilin in actin filament polymerization and severing, we hypothesized that cofilin-1 activity is regulated by Nephrin and is necessary in normal podocyte actin dynamics. Nephrin activation induced cofilin dephosphorylation via intermediaries that include phosphatidylinositol 3-kinase, SSH1, 14-3-3, and LIMK in a cell culture model. This Nephrin-induced cofilin activation required a direct interaction between Nephrin and the p85 subunit of phosphatidylinositol 3-kinase. In a similar fashion, cofilin-1 dephosphorylation was observed in a rat model of podocyte injury at a time when foot process spreading is initially observed. To investigate the necessity of cofilin-1 in the glomerulus, podocyte-specific Cfl1 null mice were generated. Cfl1 null podocytes developed normally. However, these mice developed persistent proteinuria by 3 months of age, although they did not exhibit foot process spreading until 8 months, when the rate of urinary protein excretion became more exaggerated. In a mouse model of podocyte injury, protamine sulfate perfusion of the Cfl1 mutant mouse induced a broadened and flattened foot process morphology that was distinct from that observed following perfusion of control kidneys, and mutant podocytes did not recover normal structure following additional perfusion with heparin sulfate. We conclude that cofilin-1 is necessary for maintenance of normal podocyte architecture and for actin structural changes that occur during induction and recovery from podocyte injury. 相似文献
998.
Brown rot fungi uniquely degrade wood by creating modifications thought to aid in the selective removal of polysaccharides
by an incomplete cellulase suite. This naturally successful mechanism offers potential for current bioprocessing applications.
To test the efficacy of brown rot cellulases, southern yellow pine wood blocks were first degraded by the brown rot fungus
Gloeophyllum trabeum for 0, 2, 4, and 6 weeks. Characterization of the pine constituents revealed brown rot decay patterns, with selective polysaccharide
removal as lignin compositions increased. G. trabeum liquid and solid state cellulase extracts, as well as a commercial Trichoderma reesei extract (Celluclast 1.5 L), were used to saccharify this pretreated material, using β-glucosidase amendment to remove limitation
of cellobiose-to-glucose conversion. Conditions varied according to source and concentration of cellulase extract and to pH
(3.0 vs. 4.8). Hydrolysis yields were maximized using solid state G. trabeum extracts at a pH of 4.8. However, the extent of glucose release was low and was not significantly altered when cellulase
loading levels were increased threefold. Furthermore, Celluclast 1.5 L continually outperformed G. trabeum cellulase extracts, although extent of glucose release never exceeded 22.0%. Results suggest methodological advances for
utilizing crude G. trabeum cellulases and imply that the suboptimal hydrolysis levels obtained with G. trabeum and Celluclast 1.5 L cellulases, even at high loading levels, may be due to brown rot modifications insufficiently distributed
throughout the pretreated material. 相似文献
999.
Kai Marxen Klaus Heinrich Vanselow Ralf Hintze Sebastian Lippemeier Andreas Ruser Britta Egge Franciscus Colijn Ulf-Peter Hansen 《Journal of applied phycology》2010,22(6):677-690
Two different modes of UV-B irradiation of the cyanobacterium Synechocystis sp. PCC 6803 are compared: turbidostatic control and additional physiostatic control. Under turbidostatic control, the cells
were exposed to different constant UV-B irradiances, whereas under physiostatic control, an electronic control loop modulated
UV-B irradiance in such a way that photosynthetic efficiency ϕ
PSII was kept constant at a fixed set point. The UV-B-induced stimulation of the synthesis of pigments, α-tocopherol, and the
antioxidative potential of methanolic soluble components of Synechocystis showed significant differences depending on the mode of irradiation, even though the overall doses were equal. For example,
compared to the initial values, the concentrations of myxoxanthophyll and zeaxanthin increased to 226–244% and 453% upon constant
UV-B irradiation in turbidostatic processes, whereas maxima of 600% and 740% were reached in turbidostatic process with additional
physiostatic control. The α-tocopherol concentration increased under constant UV-B irradiances, up to a maximum of 150%. Under
physiological control, however, maximum increases of 390% over the initial values were measured. Furthermore, a reaction scheme
is given explaining the higher yield under physiostatic control. 相似文献
1000.
Dominik Schilling Sven Findeiß Andreas S. Richter Jennifer A. Taylor Ulrike Gerischer 《Archives of microbiology》2010,192(9):691-702
Small non-coding RNAs (sRNAs) are key players in prokaryotic metabolic circuits, allowing the cell to adapt to changing environmental
conditions. Regulatory interference by sRNAs in cellular metabolism is often facilitated by the Sm-like protein Hfq. A search
for novel sRNAs in A. baylyi intergenic regions was performed by a biocomputational screening. One candidate, Aar, encoded between trpS and sucD showed Hfq dependency in Northern blot analysis. Aar was expressed strongly during stationary growth phase in minimal medium;
in contrast, in complex medium, strongest expression was in the exponential growth phase. Whereas over-expression of Aar in
trans did not affect bacterial growth, seven mRNA targets predicted by two in silico approaches were upregulated in stationary
growth phase. All seven mRNAs are involved in A. baylyi amino acid metabolism. A putative binding site for Lrp, the global regulator of branched-chain amino acids in E. coli, was observed within the aar gene. Both facts imply an Aar participation in amino acid metabolism. 相似文献