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181.
Washburn WN Sun CQ Bisacchi G Wu G Cheng PT Sher PM Ryono D Gavai AV Poss K Girotra RN McCann PJ Mikkilineni AB Dejneka TC Wang TC Merchant Z Morella M Arbeeny CM Harper TW Slusarchyk DA Skwish S Russell AD Allen GT Tesfamariam B Frohlich BH Abboa-Offei BE Cap M Waldron TL George RJ Young D Dickinson KE Seymour AA 《Bioorganic & medicinal chemistry letters》2004,14(13):3525-3529
A series of N-(4-hydroxy-3-methylsulfonanilidoethanol)arylglycinamides were prepared and evaluated for their human beta3 adrenergic receptor agonist activity. SAR studies led to the identification of BMS-201620 (39), a potent beta3 full agonist (Ki = 93 nM, 93% activation). Based on its favorable safety profile, BMS-201620 was chosen for clinical evaluation. 相似文献
182.
Reading SA Earley S Waldron BJ Welsh DG Brayden JE 《American journal of physiology. Heart and circulatory physiology》2005,288(5):H2055-H2061
We tested the hypothesis that TRPC3, a member of the canonical transient receptor potential (TRP) family of channels, mediates agonist-induced depolarization of arterial smooth muscle cells (SMCs). In support of this hypothesis, we observed that suppression of arterial SMC TRPC3 expression with antisense oligodeoxynucleotides significantly decreased the depolarization and constriction of intact cerebral arteries in response to UTP. In contrast, depolarization and contraction of SMCs induced by increased intravascular pressure, i.e., myogenic responses, were not altered by TRPC3 suppression. Interestingly, UTP-evoked responses were not affected by suppression of a related TRP channel, TRPC6, which was previously found to be involved in myogenic depolarization and vasoconstriction. In patch-clamp experiments, UTP activated a whole cell current that was greatly reduced or absent in TRPC3 antisense-treated SMCs. These results indicate that TRPC3 mediates UTP-induced depolarization of arterial SMCs and that TRPC3 and TRPC6 may be differentially regulated by receptor activation and mechanical stimulation, respectively. 相似文献
183.
Using the binding of a nucleotide inhibitor (guanosine-3'-monophosphate) to a ribonuclease (ribonuclease Sa) as a model system, we show that the salt-dependence of the interaction arises due to specific ion binding at the site of nucleotide binding. The presence of specific ion-protein binding is concluded from a combination of differential scanning calorimetry and NMR data. Isothermal titration calorimetry data are then fit to determine the energetic profile (enthalpy, entropy, and heat capacity) for both the ion-protein and nucleotide-protein interactions. The results provide insight into the energetics of charge-charge interactions, and have implications for the interpretation of an observed salt-dependence. Further, the presence of specific ion-binding leads to a system behavior as a function of temperature that is drastically different from that predicted from Poisson-Boltzmann calculations. 相似文献
184.
Glutaraldehyde: behavior in aqueous solution, reaction with proteins, and application to enzyme crosslinking 总被引:7,自引:0,他引:7
Glutaraldehyde possesses unique characteristics that render it one of the most effective protein crosslinking reagents. It can be present in at least 13 different forms depending on solution conditions such as pH, concentration, temperature, etc. Substantial literature is found concerning the use of glutaraldehyde for protein immobilization, yet there is no agreement about the main reactive species that participates in the crosslinking process because monomeric and polymeric forms are in equilibrium. Glutaraldehyde may react with proteins by several means such as aldol condensation or Michael-type addition, and we show here 8 different reactions for various aqueous forms of this reagent. As a result of these discrepancies and the unique characteristics of each enzyme, crosslinking procedures using glutaraldehyde are largely developed through empirical observation. The choice of the enzyme-glutaraldehyde ratio, as well as their final concentration, is critical because insolubilization of the enzyme must result in minimal distortion of its structure in order to retain catalytic activity. The purpose of this paper is to give an overview of glutaraldehyde as a crosslinking reagent by describing its structure and chemical properties in aqueous solution in an attempt to explain its high reactivity toward proteins, particularly as applied to the production of insoluble enzymes. 相似文献
185.
The mechanical properties and molecular dynamics of plant cell wall polysaccharides studied by Fourier-transform infrared spectroscopy 总被引:13,自引:0,他引:13
Wilson RH Smith AC Kacuráková M Saunders PK Wellner N Waldron KW 《Plant physiology》2000,124(1):397-406
Polarized one- and two-dimensional infrared spectra were obtained from the epidermis of onion (Allium cepa) under hydrated and mechanically stressed conditions. By Fourier-transform infrared microspectroscopy, the orientation of macromolecules in single cell walls was determined. Cellulose and pectin exhibited little orientation in native epidermal cell walls, but when a mechanical stress was placed on the tissue these molecules showed distinct reorientation as the cells were elongated. When the stress was removed the tissue recovered slightly, but a relatively large plastic deformation remained. The plastic deformation was confirmed in microscopic images by retention of some elongation of cells within the tissue and by residual molecular orientation in the infrared spectra of the cell wall. Two-dimensional infrared spectroscopy was used to determine the nature of the interaction between the polysaccharide networks during deformation. The results provide evidence that cellulose and xyloglucan associate while pectin creates an independent network that exhibits different reorientation rates in the wet onion cell walls. The pectin chains respond faster to oscillation than the more rigid cellulose. 相似文献
186.
Karanas YL Leong DS Da Lio A Waldron K Watson JP Chang H Shaw WW 《Plastic and reconstructive surgery》2003,111(3):1078-83; discussion 1084-6
The incidence of breast cancer is increasing each year. Concomitantly, cosmetic breast augmentation has become the second most often performed cosmetic surgical procedure. As the augmented patient population ages, an increasing number of breast cancer cases among previously augmented women can be anticipated. The surgical treatment of these patients is controversial, with several questions remaining unanswered. Is breast conservation therapy feasible in this patient population and can these patients retain their implants? A retrospective review of all breast cancer patients with a history of previous augmentation mammaplasty who were treated at the Revlon/UCLA Breast Center between 1991 and 2001 was performed. During the study period, 58 patients were treated. Thirty patients (52 percent) were treated with a modified radical mastectomy with implant removal. Twenty-eight patients (48 percent) underwent breast conservation therapy, which consisted of lumpectomy, axillary lymph node dissection, and radiotherapy. Twenty-two of the patients who underwent breast conservation therapy initially retained their implants. Eleven of those 22 patients (50 percent) ultimately required completion mastectomies with implant removal because of implant complications (two patients), local recurrences (five patients), or the inability to obtain negative margins (four patients). Nine additional patients experienced complications resulting from their implants, including contracture, erosion, pain, and rupture. The data illustrate that breast conservation therapy with maintenance of the implant is not ideal for the majority of augmented patients. Breast conservation therapy with explantation and mastopexy might be appropriate for rare patients with large volumes of native breast tissue. Mastectomy with immediate reconstruction might be a more suitable choice for these patients. 相似文献
187.
Wilson DF Vinogradov SA Dugan BW Biruski D Waldron L Evans SA 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2002,132(1):153-159
Oxygen dependent quenching of phosphorescence allows for non-invasive measurements of oxygen in tissue. We have designed and constructed a novel multi-frequency instrument for measurement of phosphorescence lifetimes and developed algorithms for determining the distribution of oxygen (oxygen histogram) in the microvasculature of tissue with good temporal resolution (Vinogradov et al., 2002, Compar. Biochem. A, these proceedings). This technology, in combination with a new water soluble near infra red phosphor (Oxyphor G2), was used to examine the oxygenation of subcutaneous Q7 tumors grown on the flank of Buffalo rats and their response to giving the rats oxygen or carbogen to breathe. Phosphorescence was measured using excitation at 635 nm and emission at >700 nm (the phosphorescence maximum is near 800 nm). The excitation and collection light guides were placed on the surface of the skin of the anesthetized animals separated by approximately 0.8 cm. A 6 x 6 or 7 x 7 grid (approx. 4 cm x 4 cm) was drawn on the flank and oxygen histograms were measured in each square, providing 'images' of the oxygen distribution in the tissue. This procedure determines the tissue oxygen distribution at each position in the grid. Regions of relative hypoxia (associated with the tumor) can be readily localized and the extent of hypoxia quantitatively evaluated. 相似文献
188.
Resistance to hygromycin B 总被引:11,自引:0,他引:11
C. Waldron E. B. Murphy J. L. Roberts G. D. Gustafson S. L. Armour S. K. Malcolm 《Plant molecular biology》1985,5(2):103-108
Summary A bacterial gene encoding hygromycin phosphotransferase has been modified for expression in tobacco cells. The aphIV gene from Escherichia coli was inserted between the 5 sequence of an octopine synthase gene and the 3 sequence from a nopaline synthase gene. The new gene was incorporated between T-DNA border fragments in the broad-host-range vector pKT210 to form a micro-Ti plasmid. Agrobacterium tumefaciens containing this plasmid and a Ti plasmid as helper was used to incite crown gall tumors on aseptic tobacco plants. Samples of these galls could grow in the presence of hygromycin B, provided that the aph gene had been fused with the ocs gene to maintain the sense of the coding sequences. When the genes had been fused in the reverse antisense orientation none of the gall samples could grow on hygromycin. Unlike wild-type galls the hygromycin-resistant tissue contained DNA sequences homologous to the aphIV gene. Thus the modified gene can be introduced into tobacco cells and confer on them the ability to grow in the presence of hygromycin B. 相似文献
189.
C. R. Waldron Jr. C. A. Becker-Vallone D. E. Eveleigh 《Applied microbiology and biotechnology》1986,24(6):477-486
Summary Protocols for the isolation of cellulolytic actinomycetes are described, and their use illustrated in the selection of thermophilic bacteria from soil. One isolate, Microbispora bispora, was selected for further study. It grew readily at 55°C, produced an extracellular cellulase in good yield (endoglucanase, 5.9 U/ml) that had a broad pH range (pH 5.5–7.2) and was thermally stable. Its aryl--glucosidase was cell-associated and was relatively resistant to end-product inhibition. 相似文献
190.
Vagal, nonadrenergic inhibitory system (NAIS) innervation to airway smooth muscle has been demonstrated in adults of several species, including humans. However, the functional status of this system in newborns is not known. The NAIS of intestinal smooth muscle has been demonstrated in newborns and develops in parallel with cholinergic innervation (14). Since the lung is derived embryologically from the foregut and cholinergic innervation is operative at birth, we tested the hypothesis that NAIS innervation to the airways is functional in newborn cats. Nineteen cats (2-11 days of age) were anesthetized with chloralose-urethan, and a tracheal cannula was inserted. The chest was opened and the animals were mechanically ventilated. The cervical vagus nerves were separated from the sympathetics, cut, and placed on stimulating electrodes. Mean inspiratory resistance (RL, I) and dynamic compliance (Cdyn, L) were measured on a breath-by-breath basis. Atropine and propranolol were administered (2 mg/kg iv) to block cholinergic and adrenergic pathways, respectively. Subsequently, serotonin infusion was used to increase RL, I approximately 150%. Stimulation (10 s) at frequencies ranging from 2 to 20/s caused a slow-onset (30 s to peak) long-lasting decrease in RL, I and a much smaller increase in Cdyn, L. The magnitude and duration of the bronchodilation increased with stimulus frequency to a plateau at approximately 15/s. At a stimulus frequency of 2/s, RL, I decreased 11 +/- 1.9 vs 36 +/- 4.8% (SE) at 20/s, whereas Cdyn, L increased 2 +/- 1.1 vs. 6 +/- 1.7%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献