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171.
172.
One rotary mechanism for F1-ATPase over ATP concentrations from millimolar down to nanomolar 总被引:1,自引:0,他引:1 下载免费PDF全文
Sakaki N Shimo-Kon R Adachi K Itoh H Furuike S Muneyuki E Yoshida M Kinosita K 《Biophysical journal》2005,88(3):2047-2056
F1-ATPase is a rotary molecular motor in which the central γ-subunit rotates inside a cylinder made of α3β3-subunits. The rotation is driven by ATP hydrolysis in three catalytic sites on the β-subunits. How many of the three catalytic sites are filled with a nucleotide during the course of rotation is an important yet unsettled question. Here we inquire whether F1 rotates at extremely low ATP concentrations where the site occupancy is expected to be low. We observed under an optical microscope rotation of individual F1 molecules that carried a bead duplex on the γ-subunit. Time-averaged rotation rate was proportional to the ATP concentration down to 200 pM, giving an apparent rate constant for ATP binding of 2 × 107 M−1s−1. A similar rate constant characterized bulk ATP hydrolysis in solution, which obeyed a simple Michaelis-Menten scheme between 6 mM and 60 nM ATP. F1 produced the same torque of ~40 pN·nm at 2 mM, 60 nM, and 2 nM ATP. These results point to one rotary mechanism governing the entire range of nanomolar to millimolar ATP, although a switchover between two mechanisms cannot be dismissed. Below 1 nM ATP, we observed less regular rotations, indicative of the appearance of another reaction scheme. 相似文献
173.
Biological effects of ion beams in Nicotiana tabacum L. 总被引:2,自引:0,他引:2
Yoshihiro Hase Kazuhiko Shimono Masayoshi Inoue Atsushi Tanaka Hiroshi Watanabe 《Radiation and environmental biophysics》1999,38(2):111-115
The biological effects of ion beams on Nicotiana tabacum L., particularly the induction of chromosome aberrations, were investigated. Dry seeds were exposed to 12C5+, 4He2+ and 1H+ beams with linear energy transfer (LET) ranging from 1 to 111 keV/μm and irradiated with gamma-rays. Ion beams were more
effective in reducing germination and survival of the seeds than gamma-rays. The LD50 for 12C5+ beams, 4He2+ beams and gamma-rays were 35, 60 and 500 Gy, respectively. The frequencies of mitotic cells with chromosome aberrations,
such as chromosome bridges, acentric fragments and lagging chromosomes in the root tip cells of the exposed seeds, increased
linearly with increasing doses. Relative biological effectiveness (RBE) values, based on the doses that induced a survival
inhibition of 50% and a 10% frequency of aberrant cells, were 14.3–17.5 for the 12C5+ beams, 7.0–8.3 for the 4He2+ beams and 7.8 for the 1H+ beams. Furthermore, the relative ratios of the chromosome aberration types were significantly different between the ion beam
and the gamma-ray regimes: chromosome fragments were more frequent in the former, and chromosome bridges in the latter. Based
on these results, we concluded that the repair process of initial lesions induced by ion beams may be different from that
induced by low- LET radiation.
Received: 29 October 1998 / Accepted in revised form: 25 March 1999 相似文献
174.
Takeshi Hashimoto Takumi Yokokawa Yuriko Endo Nobumasa Iwanaka Kazuhiko Higashida Sadayoshi Taguchi 《Biochemical and biophysical research communications》2013
Background
A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function.Methods
Differentiated 3T3-L1 adipocytes were incubated at 5% O2 for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC).Results
HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01).Conclusion
We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via decreased glucose uptake and lipogenic protein expression and increased basal lipolysis. Such an hypoxia-induced decrease in lipogenesis may be an attractive therapeutic target against lipid-associated metabolic diseases. 相似文献175.
Koji Ochiai Satoshi Takita Akihiko Kojima Tomohiko Eiraku Kazuhiko Iwase Tetsuya Kishi Akira Ohinata Yuichi Yageta Tokutaro Yasue David R. Adams Yasushi Kohno 《Bioorganic & medicinal chemistry letters》2013,23(1):375-381
(?)-6-(7-Methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-4-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (KCA-1490) exhibits moderate dual PDE3/4-inhibitory activity and promises as a combined bronchodilatory/anti-inflammatory agent. N-alkylation of the pyridazinone ring markedly enhances potency against PDE4 but suppresses PDE3 inhibition. Addition of a 6-aryl-4,5-dihydropyridazin-3(2H)-one extension to the N-alkyl group facilitates both enhancement of PDE4-inhibitory activity and restoration of potent PDE3 inhibition. Both dihydropyridazinone rings, in the core and extension, can be replaced by achiral 4,4-dimethylpyrazolone subunits and the core pyrazolopyridine by isosteric bicyclic heteroaromatics. In combination, these modifications afford potent dual PDE3/4 inhibitors that suppress histamine-induced bronchoconstriction in vivo and exhibit promising anti-inflammatory activity via intratracheal administration. 相似文献
176.
177.
Hisato Kobayashi Eikichi Yanagisawa Akihiko Sakashita Naoko Sugawara Shiori Kumakura Hidehiko Ogawa Hidenori Akutsu Kenichiro Hata Kazuhiko Nakabayashi Tomohiro Kono 《Epigenetics》2013,8(6):635-651
Artificial induction of active DNA demethylation appears to be a possible and useful strategy in molecular biology research and therapy development. Dimethyl sulfoxide (DMSO) was shown to cause phenotypic changes in embryonic stem cells altering the genome-wide DNA methylation profiles. Here we report that DMSO increases global and gene-specific DNA hydroxymethylation levels in pre-osteoblastic MC3T3-E1 cells. After 1 day, DMSO increased the expression of genes involved in DNA hydroxymethylation (TET) and nucleotide excision repair (GADD45) and decreased the expression of genes related to DNA methylation (Dnmt1, Dnmt3b, Hells). Already 12 hours after seeding, before first replication, DMSO increased the expression of the pro-apoptotic gene Fas and of the early osteoblastic factor Dlx5, which proved to be Tet1 dependent. At this time an increase of 5-methyl-cytosine hydroxylation (5-hmC) with a concomitant loss of methyl-cytosines on Fas and Dlx5 promoters as well as an increase in global 5-hmC and loss in global DNA methylation was observed. Time course-staining of nuclei suggested euchromatic localization of DMSO induced 5-hmC. As consequence of induced Fas expression, caspase 3/7 and 8 activities were increased indicating apoptosis. After 5 days, the effect of DMSO on promoter- and global methylation as well as on gene expression of Fas and Dlx5 and on caspases activities was reduced or reversed indicating down-regulation of apoptosis. At this time, up regulation of genes important for matrix synthesis suggests that DMSO via hydroxymethylation of the Fas promoter initially stimulates apoptosis in a subpopulation of the heterogeneous MC3T3-E1 cell line, leaving a cell population of extra-cellular matrix producing osteoblasts. 相似文献
178.
Yuji Shimizu Mio Nakazato Takaharu Sekita Koichiro Kadota Kazuhiko Arima Hironori Yamasaki Hisashi Goto Satoshi Shirahama Noboru Takamura Kiyoshi Aoyagi Takahiro Maeda 《Journal of physiological anthropology》2013,32(1):19
Background
Previous studies have reported an inverse association between height and risk of cardiovascular disease. However, evidence is limited for the association between risk of atherosclerosis and height. Further, although the association between atherosclerosis and body mass index (BMI) is reportedly positive, there have been no reports of studies on associations between height and atherosclerosis in relation to BMI.Methods
We conducted a cross-sectional study of Japanese men aged 30 to 89 years undergoing general health check-ups.Results
Of the 1,337 men, 312 were diagnosed with carotid atherosclerosis (carotid intima-media thickness (CIMT) ≥ 1.1 mm), but no significant association was found between height and carotid atherosclerosis for the entire study group. Stratification by BMI status of those analytical findings disclosed a significant inverse association between height and carotid atherosclerosis among overweight (BMI ≥ 25 kg/m2) but not among non-overweight (BMI < 25 kg/m2) men. The classical cardiovascular risk factors-adjusted odds ratio (OR) and 95% confidence interval (CI) of carotid atherosclerosis for an increment of one SD (standard deviation) in height (6.70 cm) were 0.71 (0.54 to 0.94) for overweight (BMI ≥ 25 kg/m2) and 1.05 (0.87 to 1.27) for non-overweight (BMI < 25 kg/m2) men.Conclusion
Independent from classical cardiovascular risk factors, height was found to be inversely associated with carotid atherosclerosis for overweight but not for non-overweight men. 相似文献179.
Bach1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells 总被引:4,自引:0,他引:4
180.
The hyperthermophilic endocellulase, EGPh (glycosyl hydrolase family 5) from Pyrococcus horikoshii possesses 4 cysteine residues forming 2 disulfide bonds, as identified by structural analysis. One of the disulfide bonds is located at the proximal region of the active site in EGPh, which exhibits a distinct pattern from that of the thermophilic endocellulase EGAc (glycosyl hydrolase family 5) of Acidothermus cellulolyticus despite the structural similarity between the two endocellulases. The structural similarity between EGPh and EGAc suggests that EGPh possesses a structure suitable for changing the position of the disulfide bond corresponding to that in EGAc. Introduction of this alternative disulfide bond in EGPh, while removing the original disulfide bond, did not result in a loss of enzymatic activity but the EGPh was no longer hyperthermostable. These results suggest that the contribution of disulfide bond to hyperthermostability at temperature higher than 100 °C is restrictive, and that its impact is dependent on the specific structural environment of the hyperthermophilic proteins. The data suggest that the structural position and environment of the disulfide bond has a greater effect on high-temperature thermostability of the enzyme than on the potential energy of the dihedral angle that contributes to disulfide bond cleavage. 相似文献