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81.
Vladimir L. Kolossov 《Pesticide biochemistry and physiology》2005,83(1):9-20
δ-Aminolevulinic acid (ALA) esterase(s) is an enzyme or a family of enzymes that regenerate ALA from ALA esters by hydrolysis. These enzyme(s) are highly active in cancer cells. As a consequence ALA esters have been used to advantage in ALA-dependent photoradiation therapy, since ALA esters translocate better to sites of metabolism in cancer cells and tissues than free ALA. In this work, it is shown that ALA esterase(s) also occur in insect and plant tissues, but are less active than in cancer cells. In plant cells ALA esterase activity is observed in the cytosol as well as in the plastids where most of the activity is observed in the plastid stoma. The ALA esterase activity appears to be sensitive to the nature of the esterifying alcohol as well as to components of the incubation medium. The observed lower activity of ALA ester conversion to tetrapyrroles in insect and plant cells, in comparison to free ALA, suggests that the use of ALA esters in photodynamic insecticidal and herbicidal applications may not be as advantageous as their use in cancer photodynamic therapy treatments. It is proposed that ALA esterase(s) may be involved in the mobilization of sequestered and esterified ALA. Esterification and sequestering of excess ALA may be visualized as a mean of cellular detoxification. 相似文献
82.
Sergey A. Dyshlovoy Moritz Kaune Jessica Hauschild Malte Kriegs Konstantin Hoffer Tobias Busenbender Polina A. Smirnova Maxim E. Zhidkov Ekaterina V. Poverennaya Su Jung Oh-Hohenhorst Pavel V. Spirin Vladimir S. Prassolov Derya Tilki Carsten Bokemeyer Markus Graefen Gunhild von Amsberg 《Marine drugs》2020,18(12)
Efficacy and mechanism of action of marine alkaloid 3,10-dibromofascaplysin (DBF) were investigated in human prostate cancer (PCa) cells harboring different levels of drug resistance. Anticancer activity was observed across all cell lines examined without signs of cross-resistance to androgen receptor targeting agents (ARTA) or taxane based chemotherapy. Kinome analysis followed by functional investigation identified JNK1/2 to be one of the molecular targets of DBF in 22Rv1 cells. In contrast, no activation of p38 and ERK1/2 MAPKs was observed. Inhibition of the drug-induced JNK1/2 activation or of the basal p38 activity resulted in increased cytotoxicity of DBF, whereas an active ERK1/2 was identified to be important for anticancer activity of the alkaloid. Synergistic effects of DBF were observed in combination with PARP-inhibitor olaparib most likely due to the induction of ROS production by the marine alkaloid. In addition, DBF intensified effects of platinum-based drugs cisplatin and carboplatin, and taxane derivatives docetaxel and cabazitaxel. Finally, DBF inhibited AR-signaling and resensitized AR-V7-positive 22Rv1 prostate cancer cells to enzalutamide, presumably due to AR-V7 down-regulation. These findings propose DBF to be a promising novel drug candidate for the treatment of human PCa regardless of resistance to standard therapy. 相似文献
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84.
Maxim E. Zhidkov Moritz Kaune Alexey V. Kantemirov Polina A. Smirnova Pavel V. Spirin Maria A. Sidorova Sergey A. Stadnik Elena Y. Shyrokova Dmitry N. Kaluzhny Oleg A. Tryapkin Tobias Busenbender Jessica Hauschild Tina Rohlfing Vladimir S. Prassolov Carsten Bokemeyer Markus Graefen Gunhild von Amsberg Sergey A. Dyshlovoy 《Marine drugs》2022,20(3)
Marine alkaloid fascaplysin and its derivatives are known to exhibit promising anticancer properties in vitro and in vivo. However, toxicity of these molecules to non-cancer cells was identified as a main limitation for their clinical use. Here, for the very first time, we synthesized a library of fascaplysin derivatives covering all possible substituent introduction sites, i.e., cycles A, C and E of the 12H-pyrido[1-2-a:3,4-b’]diindole system. Their selectivity towards human prostate cancer versus non-cancer cells, as well as the effects on cellular metabolism, membrane integrity, cell cycle progression, apoptosis induction and their ability to intercalate into DNA were investigated. A pronounced selectivity for cancer cells was observed for the family of di- and trisubstituted halogen derivatives (modification of cycles A and E), while a modification of cycle C resulted in a stronger activity in therapy-resistant PC-3 cells. Among others, 3,10-dibromofascaplysin exhibited the highest selectivity, presumably due to the cytostatic effects executed via the targeting of cellular metabolism. Moreover, an introduction of radical substituents at C-9, C-10 or C-10 plus C-3 resulted in a notable reduction in DNA intercalating activity and improved selectivity. Taken together, our research contributes to understanding the structure–activity relationships of fascaplysin alkaloids and defines further directions of the structural optimization. 相似文献
85.
The focusing of electric current by a single p-n junction in graphene is theoretically predicted. Precise focusing may be achieved by fine-tuning the densities of carriers on the n- and p-sides of the junction to equal values. This finding may be useful for the engineering of electronic lenses and focused beam splitters using gate-controlled n-p-n junctions in graphene-based transistors. 相似文献
86.
Kural C Kim H Syed S Goshima G Gelfand VI Selvin PR 《Science (New York, N.Y.)》2005,308(5727):1469-1472
We used fluorescence imaging with one nanometer accuracy (FIONA) to analyze organelle movement by conventional kinesin and cytoplasmic dynein in a cell. We located a green fluorescence protein (GFP)-tagged peroxisome in cultured Drosophila S2 cells to within 1.5 nanometers in 1.1 milliseconds, a 400-fold improvement in temporal resolution, sufficient to determine the average step size to be approximately 8 nanometers for both dynein and kinesin. Furthermore, we found that dynein and kinesin do not work against each other in vivo during peroxisome transport. Rather, multiple kinesins or multiple dyneins work together, producing up to 10 times the in vitro speed. 相似文献
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