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151.
152.
A detailed conformational analysis of hyperolactone C diastereomers and enantiomers ((5R,9R),(5S,9S) and (5S,9R),(5R,9S)) was done with molecular mechanics and density functional theory methods. Time-dependent density functional theory (B3PW91/TZVP) was used to calculate electronic transition energies (UV/vis spectra) and rotational strengths of the respective conformations. The effect of solvation (acetonitrile solution) on excitation energies and electronic circular dichroism was approximated by the polarizable continuum model. By comparison of the simulated CD spectrum with that measured for hyperolactone C isolated from Hypericum lloydii, its absolute configuration can be assigned as (5S,9S). 相似文献
153.
A combined experimental and quantum chemical study on the putative protonophoric activity of thiocyanate
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Inhibition of gastric acid secretion by thiocyanate is explained by a protonophoric mechanism assuming that thiocyanate induces a H(+) back flux from the acidic gastric lumen into the parietal cells of gastric mucosa. Protonophoric activity of thiocyanate was examined by swelling measurements using rat liver mitochondria and theoretically by quantum chemical methods. Mitochondria suspended in K-thiocyanate medium plus nigericin (an H/K-exchanger) swelled when the medium pH was acidic, indicating that SCN(-) initiates a transfer of H(+) across the inner membrane. To rationalize the protonophoric activity of thiocyanate, we considered the dehydration of SCN(-) to be critical for transmembranal H(+) transfer. For modeling this process, various hydrate clusters of SCN(-) and Cl(-) were generated and optimized by density functional theory (DFT) at the B3-LYP/6-311++G(d,p) level. The cluster hydration energy was lower for SCN(-) than for Cl(-). The total Gibbs free energies of hydration of the ions were estimated by a hybrid supermolecule-continuum approach based on DFT. The calculated hydration energies also led to the conclusion that SCN(-) is less efficiently solvated than Cl(-). Due to the easier removal of the hydration shell of SCN(-) relative to Cl(-), SCN(-) is favored in going across the membrane, giving rise to the protonophoric activity. 相似文献
154.
Relations in biomedical ontologies 总被引:5,自引:0,他引:5
Smith B Ceusters W Klagges B Köhler J Kumar A Lomax J Mungall C Neuhaus F Rector AL Rosse C 《Genome biology》2005,6(5):R46-15
To enhance the treatment of relations in biomedical ontologies we advance a methodology for providing consistent and unambiguous formal definitions of the relational expressions used in such ontologies in a way designed to assist developers and users in avoiding errors in coding and annotation. The resulting Relation Ontology can promote interoperability of ontologies and support new types of automated reasoning about the spatial and temporal dimensions of biological and medical phenomena. 相似文献
155.
Three forms of cytochrome c oxidase, fully oxidized CcO (CcO-O), oxidized CcO complexed with cyanide (CcO.CN), and mixed valence CcO, in which both heme a(3) and Cu(B) are reduced and stabilized by carbon monoxide (MV.CO), were investigated by optical spectroscopy, MCD, and stopped-flow for the pH sensitivity of spectral features. In the pH range between pH 5.7 and 9.0, both heme a and heme a(3) in CcO-O interact with a single protolytic group. From the variation of the position of the Soret peak with changes in pH, a pK(a) of 6.6 +/- 0.2 was determined for this group. The pH sensitivity of heme a(3) is lost in the CcO.CN complex, and only heme a responds to pH changes. In MV.CO the spectra of both hemes are almost independent of pH between 5.7 and 11.0. The stoichiometry of proton uptake in the conversion of CcO-O both to MV.CO and to fully reduced CcO was determined between pH 5.8 and pH 8.2. Formation of MV.CO from CcO-O was accompanied by the uptake of approximately two protons, and this value was almost independent of pH. Full reduction of oxidized CcO was associated with the uptake of approximately 2 H(+) at basic pH, and this value increases with decreasing pH. On the basis of these proton uptake measurements, it is concluded that the pK(a) of the group is independent of the redox state of CcO. It is suggested that Glu60 of subunit II, located at the entrance of the proton conducting K-channel, is the protolytic residue that interacts with both hemes through a hydrogen-bonding network. 相似文献
156.
An interaction between cytochrome a in oxidized cytochrome c oxidase (CcO) and anions has been characterized by EPR spectroscopy. Those anions that affect the EPR g = 3 signal of cytochrome a can be divided into two groups. One group consists of halides (Cl-, Br-, and I-) and induces an upfield shift of the g = 3 signal. Nitrogen-containing anions (CN-, NO2-, N3-, NO3-) are in the second group and shift the g = 3 signal downfield. The shifts in the EPR spectrum of CcO are unrelated to ligand binding to the binuclear center. The binding properties of one representative from each group, azide and chloride, were characterized in detail. The dependence of the shift on chloride concentration is consistent with a single binding site in the isolated oxidized enzyme with a Kd of approximately 3 mm. In mitochondria, the apparent Kd was found to be about four times larger than that of the isolated enzyme. The data indicate it is the chloride anion that is bound to CcO, and there is a hydrophilic size-selective access channel to this site from the cytosolic side of the mitochondrial membrane. An observed competition between azide and chloride is interpreted by azide binding to three sites: two that are apparent in the x-ray structure plus the chloride-binding site. It is suggested that either Mg2+ or Arg-438/Arg-439 is the chloride-binding site, and a mechanism for the ligand-induced shift of the g = 3 signal is proposed. 相似文献
157.
Fabian Schmeling Gert Stange Uwe Homberg 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2010,196(3):199-211
Studies on the generation of rhythmic motor patterns have shown that peripheral sensory input may contribute substantially
to the rhythm generating network. A prominent example is the wing beat frequency of desert locusts, which can be entrained
to rhythmic mechanosensory input, but also to the frequency of periodic light flashes. To further analyze the entrainment
by light, tethered flying locusts were presented with periodic light flashes, while the position of the forewing was filmed.
We show that entrainment of wing beat occurs both in the UV and green range of light. Animals maintained a characteristic
phase relationship to the light stimulus with the most elevated wing position occurring at the end of the dark phase. Speed
and time course of entrainment varied greatly and ranged from the duration of a single wing beat cycle to several seconds.
To identify the visual system mediating entrainment, synchronization to UV light was tested after cutting the optic stalks
to the optic lobes/compound eyes or the ocellar nerves. The results show that light entrainment of the locust flight pattern
is largely and perhaps exclusively mediated via the fast ocellar pathway and may have a role to stabilize flight with respect
to the horizon. 相似文献
158.
Ana María Calderoni Verónica Biaggio Mariano Acosta Liliana Oliveros Fabian Mohamed María Sofía Giménez 《Biometals》2010,23(1):135-143
Cadmium (Cd) is widely used in industrial applications and is an important contaminant of agricultural products. As an endocrine
disruptor, Cd modifies the hormone release of pituitary anterior lobe (PAL). This work was undertaken to evaluate a possible
association between phospholipase D (PLD) and prolactin mRNA expressions and the activity of lactotrophs and folliculostellate
cells (FSC) in PAL of Cd exposed adult male Wistar rats (Cd, 0.133 mM per liter for 2 months). The PALs were submitted to
immunohistochemical and morphometric analysis to determine the percentage of lactotrophs (PRL-ir) and FSC (S-100-ir). Cultured
PAL cells were stained with Hoechst 33258 to determine the presence of alterations in nuclear morphology consistent with apoptosis.
The expressions of PLD and prolactin mRNA were assessed by RT-PCR. Cd treated rats showed a decrease of PLD mRNA levels that
can be associated to both high number of apoptotic cells and increase of S-100 protein expression in FSC. Cd decreased prolactin
mRNA expression, number of lactotrophs and percentage of PRL-ir suggesting a low availability of prolactin to be secreted
from PAL. Cd modifies the lactotrophs activity of pituitary gland through biochemical, genomic and morphological changes and
contributes directly or indirectly to the levels of serum prolactin. 相似文献
159.
Fabian Krauth Hans-Martin Dahse Hans-Hermann Rüttinger Petra Frohberg 《Bioorganic & medicinal chemistry》2010,18(5):1816-1821
A series of novel small molecules with a 1,2,4-triazine scaffold was obtained according to a recently published and highly efficient synthetic route. Screening for antiproliferative and cytotoxic activity revealed distinct anticancer effects against the human leukemia cell line K-562 combined with a remarkable low cytotoxicity. All compounds were in agreement with the ‘rule-of-five’ claims by Lipinski and calculated log Pcalc values were experimentally confirmed (log Pexp). For the most active compounds, in vitro serum albumin binding was investigated and structure–activity relationships were established. 相似文献
160.
Ruan W Fahlbusch F Clemmons DR Monaco ME Walden PD Silva AP Schmid HA Kleinberg DL 《Molecular endocrinology (Baltimore, Md.)》2006,20(2):426-436
Somatostatin analogs (SAs) treat acromegaly by lowering pituitary GH secretion, which, in turn, lowers systemic IGF-I. The profound systemic effect is often greater than expected in the face of only partial GH suppression. Here we report that the SA SOM230 can also act by a nonpituitary-mediated inhibition of IGF-I action. SOM230 inhibited mammary development in intact and hypophysectomized female rats, a process requiring IGF-I. IGF-I overcame this inhibition. SOM230 also inhibited other actions of IGF-I (inhibition of apoptosis, phosphorylation of insulin receptor substrate-1, and cell division). SOM230 did not reduce IGF-I mRNA abundance in mammary gland but did stimulate IGF binding protein 5 (IGFBP5). IGFBP5 was 3.75 times higher in mammary epithelium of SOM230 than in placebo animals (P < 0.001). Administration of IGFBP-5 also inhibited GH-induced mammary development (P < 0.001). Measurement of sstr(1-5) (somatostatin subtype receptor) by real-time RT-PCR revealed that the mammary glands had an abundance of sstr(3) and lower amounts of sstr(4) and sstr(5) but no sstr(1) or sstr(2.) That mammary development was also inhibited to a lesser degree than SOM230 by octreotide, whose main action is through sstr(2), strongly suggests that sstr(3) is at least in part mediating the effects of the SAs. We conclude that 1) SAs inhibit IGF-I action in the mammary gland through a novel nonpituitary mechanism; 2) IGFBP-5, here shown to inhibit pubertal mammary development, might mediate the effect; and 3) Measurement of available sstr receptors in the mammary gland suggests that sstr(3) mediates the SA activity, but sstr(5) is also a possible mediator. 相似文献