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941.
Yoshiko Kagoshima Makoto Mori Eiko Suzuki Takahiro Shibayama Tamako Iida Yasuki Kamai Toshiyuki Konosu 《Bioorganic & medicinal chemistry letters》2009,19(13):3559-3563
In this study, the synthesis and evaluation of a number of esters of CS-758 as injectable prodrugs are described. Phosphoryl ester 1a was soluble in water (>30 mg/mL) and was converted to CS-758 in human liver microsome. It was also converted to CS-758 in rats after iv administration, wherein the bioavailability of CS-758 was 53%. Compound 1a (iv) reduced the viable cell counts in kidneys in a murine systemic Candida albicans infection model, wherein the effect was comparable to or slightly superior to that of CS-758 (po). The prodrug 1a proved to be a promising injectable antifungal agent whose further evaluation is warranted. 相似文献
942.
943.
944.
Masato Irisawa Jun Inoue Nozomi Ozawa Kazutoshi Mori Ryuichiro Sato 《The Journal of biological chemistry》2009,284(42):28995-29004
945.
Reiko Sakaguchi Takashi Endoh Seigo Yamamoto Kazuki Tainaka Kenji Sugimoto Nobutaka Fujieda Shigeki Kiyonaka Yasuo Mori Takashi Morii 《Bioorganic & medicinal chemistry》2009,17(20):7381-7386
A fluorescent sensor for the detection of inositol-1,3,4,5-tetrakisphosphate, Ins(1,3,4,5)P4, was constructed from a split PH domain and a single circularly permuted GFP. A structure-based design was conducted to transduce a ligand-induced subtle structural perturbation of the split PH domain to an alteration in the population of the protonated and the deprotonated states of the GFP chromophore. Excitation of each distinct absorption band corresponding to the protonated or the deprotonated state of GFP resulted an increase and a decrease, respectively, in the intensity of emission spectra upon addition of Ins(1,3,4,5)P4 to the split PH domain-based sensor. The Ins(1,3,4,5)P4 sensor retained the ligand affinity and the selectivity of the parent PH domain, and realized the ratiometric fluorescence detection of Ins(1,3,4,5)P4. 相似文献
946.
Adenosine 5'-triphosphate (ATP) generation is an essential biological reaction for all living cells. Recently, we developed a Permeable Cell Assay for high-throughput measurement of cellular ATP synthetic activity, mainly resulting from glycolysis [Hara, K.Y., Mori, H., 2006. An efficient method for quantitative determination of cellular ATP synthetic activity. J. Biomol. Screen. 11, 310-317]. By using this method, we determined the cellular ATP synthetic activity in the stationary phase of a complete set of single-gene deletion strains of Escherichia coli. Their activities ranged from a minimum of 2% to a maximum of 445%, relative to parental strains. Deletions of metabolism-related genes frequently caused an increase in the rate of ATP synthetic activity, while activity was reduced by deletions of a variety of functional genes, including many poorly characterized genes. We also demonstrated that the deletion of the ptsG gene doubled ATP-driven glutathione synthesis and increased cellular ATP synthetic activity. Our study also indicated that it should be easy to obtain active strains for ATP synthesis from deletion strains. Overall, the data set of this study may be useful to improve E. coli strains for ATP-dependent industrial processes and, therefore, may be important for the design of so-called cell factories. 相似文献
947.
948.
Toshiaki Mori Momoko Toyoda Tatsuro Ohtsuka Yoshio Okahata 《Analytical biochemistry》2009,395(2):211-216
A biotinylated mannotriose (Man3-bio) was dispersively immobilized in the matrix of biotinylated lactose (Gal-Glc-bio) on a streptavidin-covered, 27-MHz quartz crystal microbalance (QCM), and binding kinetics of concanavalin A (Con A) to Man3-bio in the Gal-Glc-bio matrix could be obtained from frequency decreases (mass increases) of the QCM. Association constants (Ka) and binding and dissociation rate constants (kon and koff) could be determined separately as the 1:1 and 1:2 bindings of Con A to Man3-bio on the surface. When Man3-bio was immobilized with content of 1 to 5 mol% in the matrix, the 1:1 binding of Con A to Man3-bio was obtained as Ka = (4 ± 1) × 106 M−1, kon = (4 ± 1) × 104 M−1 s−1, and koff = (12 ± 2) × 10–3 s−1. On the contrary, when Man3-bio was immobilized with content of 20 to 100 mol% in the matrix, the 1:2 binding of Con A to Man3-bio was obtained as Ka = (14 ± 2) × 106 M−1, kon = (14 ± 2) × 104 M−1 s−1, and koff = (7 ± 2) × 10–3 s−1. Thus, Ka for the 1:2 binding was 10 times larger than that for the 1:1 binding, with a three times larger binding rate constant (kon) and a three times smaller dissociation rate constant (koff). This is the first example to obtain separate kinetic parameters for the 1:1 and 1:2 bindings of lectins to carbohydrates on the surface. 相似文献
949.
Pan Y Iwata F Wang D Muraguchi M Ooga K Ohmoto Y Takai M Cho G Kang J Shono M Li XJ Okamura K Mori T Ishikawa Y 《Biochimica et biophysica acta》2009,1790(1):49-56
BACKGROUND: It is unknown whether AQP5 and lipid rafts are released into human unstimulated (resting) saliva and saliva in response to secretagogues. METHODS: In order to quantitate the salivary concentration of AQP5, we produced a polyclonal antibody for human AQP5 and developed an enzyme-like immunosorbent assay (ELISA). RESULTS: AQP5 and lipid rafts were identified in human resting saliva. The amount of AQP5 in resting saliva showed a diurnal variation with high levels during waking hours, and an age-related decrease in AQP5 was coincident with the volume of resting saliva. Cevimeline, a muscarinic acetylcholine receptor (mAChR) agonist, induced the release of AQP5 with lipid rafts, amylase, mucin, and lysozyme. Changes in saliva AQP5 levels after cevimeline administration occurred simultaneously with changes in saliva flow rates. Confocal microscopy revealed that AQP5 was located in the apical plasma membrane and showed a diffuse pattern in parotid glands under resting conditions. Following cevimeline administration, AQP5 was predominantly associated with the APM and was localized in the lumen. GENERAL SIGNIFICANCE: AQP5 and lipid rafts were released with salivary proteins from human salivary glands by the stimulation of M3 mAChRs, and that changes in saliva AQP5 levels can be used as an indicator of salivary flow rate and also as a useful index of M3 mAChR agonist's action on human salivary glands. 相似文献
950.
Miyuki Kuno Hiroyuki Ando Hirokazu Morihata Hiromu Sakai Hiroyuki Mori Makoto Sawada Shigetoshi Oiki 《The Journal of general physiology》2009,134(3):191-205
Voltage-gated proton channels are found in many different types of cells, where they facilitate proton movement through the membrane. The mechanism of proton permeation through the channel is an issue of long-term interest, but it remains an open question. To address this issue, we examined the temperature dependence of proton permeation. Under whole cell recordings, rapid temperature changes within a few milliseconds were imposed. This method allowed for the measurement of current amplitudes immediately before and after a temperature jump, from which the ratios of these currents (Iratio) were determined. The use of Iratio for evaluating the temperature dependence minimized the contributions of factors other than permeation. Temperature jumps of various degrees (ΔT, −15 to 15°C) were applied over a wide temperature range (4–49°C), and the Q10s for the proton currents were evaluated from the Iratios. Q10 exhibited a high temperature dependence, varying from 2.2 at 10°C to 1.3 at 40°C. This implies that processes with different temperature dependencies underlie the observed Q10. A novel resistivity pulse method revealed that the access resistance with its low temperature dependence predominated in high temperature ranges. The measured temperature dependence of Q10 was decomposed into Q10 of the channel and of the access resistances. Finally, the Q10 for proton permeation through the voltage-gated proton channel itself was calculated and found to vary from 2.8 at 5°C to 2.2 at 45°C, as expected for an activation enthalpy of 64 kJ/mol. The thermodynamic features for proton permeation through proton-selective channels were discussed for the underlying mechanism. 相似文献