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201.
Tsuzuki Y Nguyen TK Garud DR Kuberan B Koketsu M 《Bioorganic & medicinal chemistry letters》2010,20(24):7269-7273
Various 4-deoxy-4-fluoro-xylosides were prepared using click chemistry for evaluating their potential utility as inhibitors of glycosaminoglycan biosynthesis. 2,3-Di-O-benzoyl-4-deoxy-4-fluoro-β-D-xylopyranosylazide, obtained from L-arabinopyranose by six steps, was treated with a wide variety of azide-reactive triple bond-containing hydrophobic agents in the presence of Cu(2+) salt/ascorbic acid, a step known as click chemistry. After click chemistry, benzoylated derivatives were deprotected under Zemplén conditions to obtain 4-deoxy-4-fluoro-xyloside derivatives. A mixture of α:β-isomers of twelve derivatives were then separated on a reverse phase C18 column using HPLC and the resulting twenty four 4-deoxy-4-fluoro-xylosides were evaluated for their ability to inhibit glycosaminoglycan biosynthesis in endothelial cells. We identified two xyloside derivatives that selectively inhibit heparan sulfate and chondroitin sulfate/derman sulfate biosynthesis without affecting cell viability. These novel derivatives can potentially be used to define the biological actions of proteoglycans in model organisms and also as therapeutic agents to combat various human diseases in which glycosaminoglycans participate. 相似文献
202.
Yasuto Tsuruta Kiyoshi Maruyama Hirofumi Inoue Keiko Kosha Yuuko Date Nobuyuki Okamura Seiji Eto Eijiro Kojima 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(3-4):327-332
A simple and highly sensitive high-performance liquid chromatography procedure was developed for the determination of carnosine in urine. Carnosine was derivatized with 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride at 70 °C for 15 min in borate buffer (20 mmol l?1, pH 9.0) to produce fluorescent sulfonamides. After hydrolysis of the reaction mixture with formic acid at 100 °C for 15 min, the fluorescent derivative of carnosine was separated on a reversed-phase column with a linear gradient elution using solvents of (A) acetate buffer (0.1 mmol l?1, pH 7.0) and (B) acetonitrile at a flow-rate of 1.0 ml/min and was detected at excitation and emission wavelengths of 318 and 400 nm, respectively. The detection limit of carnosine was 4 fmol at a signal-to-noise ratio of 3. The within-day and day-to-day relative standard deviations were 2.7–4.6% and 0.4–5.2%, respectively. The concentration of carnosine in normal human urine was found to be 4.6–125 nmol (mg creatinine)?1 (mean ± SD: 21.6 ± 26.6 nmol (mg creatinine)?1, n = 20). 相似文献
203.
Kohshi Kinkawa Shin Watanabe Kyozo Hayashi Seiji Inoue 《Biochemical and biophysical research communications》2010,395(3):377-381
Venomous snakes such as Gloydius brevicaudus have three distinct types of phospholipase A2 inhibitors (PLIα, PLIβ, and PLIγ) in their blood so as to protect themselves from their own venom phospholipases A2 (PLA2s). Expressions of these PLIs in G. brevicaudus liver were found to be enhanced by the intramuscular injection of its own venom. The enhancement of gene expressions of PLIα and PLIβ in the liver was also found to be induced by acidic PLA2 contained in this venom. Furthermore, these effects of acidic PLA2 on gene expression of PLIs were shown to be unrelated to its enzymatic activity. These results suggest that these venomous snakes have developed the self-protective system against their own venom, by which the venom components up-regulate the expression of anti-venom proteins in their liver. 相似文献
204.
205.
Seiji Abe Shigeo Nakabayashi Jun‐Ichiro Murayama Yoshihiro Sano Ken‐Ichi Ohno Masako Maeda Hidetoshi Arakawa 《Luminescence》2010,25(6):456-462
Nitric oxide (NO) is related to various physiological effects as well as to numerous diseases caused by accentuation of NO production. Measurement of NO in cells and tissues is difficult as NO readily reacts with other molecules; furthermore, its half‐life as a radical is fleeting. Currently, many NO pharmaceuticals are marketed as therapeutic agents for ischemic disease. Consequently, the identification of NO radicals and determination of generation rate from pharmaceuticals is very important when the effect of the medicinal supply is estimated. In this study, we developed a fluorometric assay for NO employing sesamol (3,4‐methylenedioxyphenol) as a fluorometric substrate. Sesamol is converted to a fluorescent derivative (ex. 365 nm, em. 447 nm), which is dimmer in the presence of NO. The detection limit of NO with this method is 400 fmol; moreover, NO generated from drugs can be measured. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
206.
Motoyuki Iemitsu Seiji Maeda Subrina Jesmin Takeshi Otsuki Yoshitoshi Kasuya Takashi Miyauchi 《Journal of applied physiology》2006,101(1):151-163
Since exercise training causes cardiac hypertrophy and a single bout induces mechanical stress to the heart, the present study aimed to characterize the activation patterns of multiple MAPK signaling pathways in the heart after a single bout of exercise or chronic exercises. The hearts of untrained rats received 5, 15, and 30 min of treadmill running exercise (Ex5 to Ex30) and rested for 0.5, 1, 3, 6, 12, and 24 h (PostEx0.5 to PostEx24) before subjecting them to the following different experiments. Activation of MAPKs (ERK, JNK, and p38) and MAPKKs (MEK1/2, SEK, and MKK3/6) increased immediately after acute exercise in a time-dependent manner, with ERK, JNK, and p38 peaking at Ex15, Ex15, and Ex30, respectively. Expression of immediate early genes (c-fos, c-jun, and c-myc) was augmented and activator protein-1 DNA binding activity was enhanced in untrained rats immediately after a single bout of exercise. The elevated levels of MAPKs declined to the resting levels within 24 h after exercise. In another set of experiments, following 4, 8, and 12 wk of exercise training, the rats exhibited significant cardiac hypertrophy by week 12. Activation of MAPKs in the 4-wk-trained rats increased after a 30-min single bout of exercise but decreased in the 8-wk group. Finally, the activity of MAPKs signaling in the 12-wk-trained rats exposed to an acute bout of exercise was unaltered. We conclude that exercise induces the activation of multiple MAPK (ERK, JNK, and p38) pathways in the heart, an effect that gradually declines with the development of exercise-induced cardiac hypertrophy. 相似文献
207.
208.
Kumai T Takeba Y Matsumoto N Nakaya S Tsuzuki Y Yanagida Y Hayashi M Kobayashi S 《Life sciences》2007,81(15):1193-1198
We investigated the effects of fasudil, a Rho kinase inhibitor, on hypertension in spontaneously hypertensive rats and on the catecholamine synthetic pathway. Ten-week-old male SHR and Wistar-Kyoto rats were administered fasudil (10 mg/kg/day s.c.) for 4 days. Systolic blood pressure was measured using the tail-cuff method. Catecholamine levels were measured with high-performance liquid chromatography-ECD methods. Tyrosine hydroxylase protein levels were measured in Western blot analysis. The tyrosine hydroxylase mRNA level was measured using real-time PCR methods. Fasudil significantly decreased systolic blood pressure in spontaneously hypertensive rats, but not in Wistar-Kyoto rats. Fasudil also significantly decreased catecholamine, tyrosine hydroxylase protein, and tyrosine hydroxylase mRNA levels in the adrenal medulla of spontaneously hypertensive rats. These results suggest that the depressor effects of fasudil on hypertension in spontaneously hypertensive rats may be related to inhibition of the catecholamine synthetic pathway. 相似文献
209.
210.
Abe T Kakehata S Kitani R Maruya S Navaratnam D Santos-Sacchi J Shinkawa H 《The Journal of membrane biology》2007,215(1):49-56
The development of motor protein activity in the lateral membrane of the mouse outer hair cell (OHC) from postnatal day 5
(P5) to P18 was investigated under whole-cell voltage clamp. Voltage-dependent, nonlinear capacitance (C
v), which represents the conformational fluctuations of the motor molecule, progressively increased during development. At
P12, the onset of hearing in the mouse, C
v was about 70% of the mature level. C
v saturated at P18 when hearing shows full maturation. On the other hand, C
lin, which represents the membrane area of the OHC, showed a relatively small increase with development, reaching steady state
at P10. This early maturation of linear capacitance is further supported by morphological estimates of surface area during
development. These results, in light of recent prestin knockout experiments and our results with quantitative polymerase chain
reaction, suggest that, rather than the incorporation of new motors into the lateral membrane after P10, molecular motors
mature to augment nonlinear capacitance. Thus, current estimates of motor protein density based on charge movement may be
exaggerated. A corresponding indicator of motor maturation, the motor’s operating voltage midpoint, V
pkcm, tended to shift to depolarized potentials during postnatal development, although it was unstable prior to P10. However,
after P14, V
pkcm reached a steady-state level near −67 mV, suggesting that intrinsic membrane tension or intracellular chloride, each of which can modulate V
pkcm, may mature at P14. These developmental data significantly alter our understanding of the cellular mechanisms that control
cochlear amplification and provide a foundation for future analysis of genetic modifications of mouse auditory development. 相似文献