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991.
Hidefumi Yoshinaga Shuji Masumoto Koji Koyama Naoya Kinomura Yuji Matsumoto Taro Kato Satoko Baba Kenji Matsumoto Tomoko Horisawa Hitomi Oki Kazuki Yabuuchi Toru Kodo 《Bioorganic & medicinal chemistry》2017,25(1):293-304
We report the discovery of a novel benzylpiperidine derivative with serotonin transporter (SERT) inhibitory activity and 5-HT1A receptor weak partial agonistic activity showing the antidepressant-like effect. The 3-methoxyphenyl group and the phenethyl group of compound 1, which has weak SERT binding activity, but potent 5-HT1A binding activity, were optimized, leading to compound 35 with potent and balanced dual SERT and 5-HT1A binding activity, but also potent CYP2D6 inhibitory activity. Replacement of the methoxy group in the left part of compound 35 with a larger alkoxy group, such as ethoxy, isopropoxy or methoxy-ethoxy group ameliorated CYP2D6 inhibition, giving SMP-304 as a candidate. SMP-304 with serotonin uptake inhibitory activity and 5-HT1A weak partial agonistic activity, which could work as a 5-HT1A antagonist, displayed faster onset of antidepressant-like effect than a representative SSRI paroxetine in an animal model. 相似文献
992.
993.
Hideaki Takano Yuhei Matsui Junpei Nomura Masahiro Fujimoto Naoto Katsumata Takafumi Koyama 《Bioscience, biotechnology, and biochemistry》2017,81(1):153-164
AmfS, a class III lantipeptide serves as a morphogen in Streptomyces griseus. Here, we constructed a high production system of AmfS in S. griseus. We isolated S. griseus Grd1 strain defective in glucose repression of aerial mycelium formation and found it suitable for the overproduction of AmfS. Two expression vectors carrying the strong and constitutive ermE2 promoter were constructed using a multicopy number plasmid, pIJ702. The use of the Grd1 strain combined with the expression vectors enabled high production of AmfS by S. griseus into its culture broth. The expression system was also effective for the generation of abundant AmfS derived from Streptomyces avermitilis. In addition, site-directed mutagenesis revealed the amino acid residues essential for the morphogen activity of AmfS. These results indicate that the constructed system enables efficient production of class III lantipeptides by Streptomyces. 相似文献
994.
Heat Stress Modulates Both Anabolic and Catabolic Signaling Pathways Preventing Dexamethasone‐Induced Muscle Atrophy In Vitro
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Wakako Tsuchida Masahiro Iwata Takayuki Akimoto Shingo Matsuo Yuji Asai Shigeyuki Suzuki 《Journal of cellular physiology》2017,232(3):650-664
It is generally recognized that synthetic glucocorticoids induce skeletal muscle weakness, and endogenous glucocorticoid levels increase in patients with muscle atrophy. It is reported that heat stress attenuates glucocorticoid‐induced muscle atrophy; however, the mechanisms involved are unknown. Therefore, we examined the mechanisms underlying the effects of heat stress against glucocorticoid‐induced muscle atrophy using C2C12 myotubes in vitro, focusing on expression of key molecules and signaling pathways involved in regulating protein synthesis and degradation. The synthetic glucocorticoid dexamethasone decreased myotube diameter and protein content, and heat stress prevented the morphological and biochemical glucocorticoid effects. Heat stress also attenuated increases in mRNAs of regulated in development and DNA damage responses 1 (REDD1) and Kruppel‐like factor 15 (KLF15). Heat stress recovered the dexamethasone‐induced inhibition of PI3K/Akt signaling. These data suggest that changes in anabolic and catabolic signals are involved in heat stress‐induced protection against glucocorticoid‐induced muscle atrophy. These results have a potentially broad clinical impact because elevated glucocorticoid levels are implicated in a wide range of diseases associated with muscle wasting. J. Cell. Physiol. 232: 650–664, 2017. © 2016 The Authors. Journal of Cellular Physiology published by Wiley Periodicals, Inc. 相似文献
995.
Shimpei Oikawa Hitomi Ehara Mika Koyama Tadaki Hirose Kouki Hikosaka Charles P. Chen Hirofumi Nakamura Hidemitsu Sakai Takeshi Tokida Yasuhiro Usui Toshihiro Hasegawa 《Plant and Soil》2017,413(1-2):231-242
Background and Aims
The effects of Sb(V), alone or combined with Se, on the growth and root development of plants are unknown. The aim of this study is to investigate the interaction between selenite and different forms of Sb and the effects on their uptake in rice and on rice root morphology.Methods
A hydroponic experiment was conducted that contained fourteen treatments. The treatment levels for Se were 0.5 and 1 mg L?1, and the treatment levels for Sb(III) and Sb(V) were 5 and 15 mg L?1.Results
Sb(V) alone significantly reduced the surface area, mean diameter and volume of the roots, whereas Sb(III) alone reduced the values of most parameters of root morphology. The addition of 1 mg L?1 Se significantly enhanced the surface area, number of medium roots, and Sb concentration in the roots subjected to 15 mg L?1 Sb(V), but it decreased the number of root forks, the number and proportion of fine roots, and the shoot Sb concentration under exposure to 15 mg L?1 Sb(III). When the plants were subjected to 1 mg L?1 Se, the addition of 15 mg L?1 Sb(III) markedly reduced the shoot and root Se concentrations and the number of root tips, root forks, and fine roots and increased the mean root diameter. However, the addition of Sb(V) did not significantly affect the root and shoot Se concentrations but significantly decreased the number of root forks and fine roots and increased the proportion of medium roots.Conclusions
Se and Sb(III) showed antagonistic effects on uptake in the shoots, but not in the roots, of paddy rice. A range of Se concentrations could stimulate the uptake of Sb in both the shoots and roots of paddy rice exposed to Sb(V).996.
In the black chafer Holotrichia kiotonensis Brenske (Coleoptera: Scarabaeidae), mating behavior was observed between 1940 and 2010 hours at < 0.1 lx in both the laboratory and the field. In the laboratory, an ether extract of female abdominal glands induced a series of pre-mating behaviors such as short-distance orientation and abdominal bending. When the extract was fractionated by silica gel column chromatography, the active fraction was eluted with 50% ether in hexane and 100% ether. Gas chromatography–mass spectrometry analysis revealed that both active fractions contained anthranilic acid (2-amino-benzoic acid) as a major compound. The amount of this compound was determined to be ca. 600 ng/female by high performance liquid chromatography analysis with a fluorescence detector. In the field, male chafers were observed to land on cotton balls impregnated with 10 mg of authentic anthranilic acid. When a white ball treated with anthranilic acid was placed 2–10 cm away from an untreated black ball, males were observed to land significantly more frequently on the latter. These results suggest that males could recognize white balls below 0.1 lx and landed on black balls. When a treated black ball was placed beside an untreated black ball, more males landed on the former. The difference was significant when the distance between the two lures was 5 or 10 cm, but not significant when it was 2 cm. These observations demonstrated that anthranilic acid was the sex-attractant pheromone for the black chafer H. kiotonensis and that the males located and landed on a pheromone source by using olfaction in conjunction with visual orientation. The importance of visual orientation in this nocturnal species is discussed in comparison with the congeneric diurnal species Holotrichia loochooana loochooana. 相似文献
997.
Suman?Chandra?Nath Eiji?Nagamori Masanobu?Horie Masahiro?Kino-okaEmail author 《Bioprocess and biosystems engineering》2017,40(1):123-131
Human induced pluripotent stem cells (hiPSCs) secrete essential autocrine factors that are removed along with toxic metabolites when the growth medium is exchanged daily. In this study, after determining the minimum inhibitory level of lactic acid for hiPSCs, a medium refining system was constructed by which toxic metabolites were removed from used culture medium and autocrine factors as well as other growth factors were recycled. Specifically, about 87 % of the basic fibroblast growth factor and 80 % of transforming growth factor beta 1 were retained in the refined medium after dialysis. The refined medium efficiently potentiated the proliferation of hiPS cells in adherent culture. When the refining system was used to refresh medium in suspension culture, a final cell density of (1.1 ± 0.1) × 106 cells mL?1 was obtained, with 99.5 ± 0.2 % OCT 3/4 and 78.3 ± 1.1 % TRA-1-60 expression, on day 4 of culture. These levels of expression were similar to those observed in the conventional suspension culture. With this method, culture medium refinement by dialysis was established to remove toxic metabolites, recycle autocrine factors as well as other growth factors, and reduce the use of macromolecules for the expansion of hiPSCs in suspension culture. 相似文献
998.
The increased atmospheric deposition of nitrogen (N) may indirectly affect herbivorous insects by deposition-induced changes in host quantity and quality. To avoid the “lamp effect” that can occur in small-scale N fertilizations, large-scale N fertilization (ca. 9 ha, 100 kg N ha?1 year?1) experiments were performed in a deciduous, broad-leaved, cool temperate forest. The initial responses of mature oak canopy trees (Quercus crispula) and their herbivorous insects to N fertilization were evaluated by measuring the growth and leaf qualities of the trees. The feeding guilds and community structures of the herbivorous insects at control and fertilized sites before (2012) and after (2013–2014) N fertilization were then determined. In 2014, N fertilization enhanced plant growth. In 2013 but not 2014, N fertilization increased N content and decreased the carbon/nitrogen (C/N) ratio in leaves. Despite these changes in plant traits in 2013, N fertilization had no effect on either feeding guilds (chewing herbivory, galler density, and miner density) or community structures (species richness, diversity index, and relative abundance) of herbivorous insects in the same year. However, in 2014, the diversity index decreased significantly, whereas species richness and abundance were unchanged. This suggests that species-specific responses to changes in leaf qualities following N fertilization, in the form of altered insect fecundity, impact the diversity index of herbivorous insects, albeit with a 1-year lag time. Thus, our large-scale N fertilization experiment show the time-delayed bottom-up effects of N fertilization on insect community structure. 相似文献
999.
Basic research on pluripotent stem cells is designed to enhance understanding of embryogenesis, whereas applied research is designed to develop novel therapies and prevent diseases. Attainment of these goals has been enhanced by the establishment of embryonic stem cell lines, the technological development of genomic reprogramming to generate induced-pluripotent stem cells, and improvements in vitro techniques to manipulate stem cells. This review summarizes the techniques required to generate neural cells from pluripotent stem cells. In particular, this review describes current research applications of a simple neural differentiation method, the neural stem sphere method, which we developed. 相似文献
1000.