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Angela Clements David Allsop Dominic M. Walsh Carvell H. Williams 《Journal of neurochemistry》1996,66(2):740-747
Abstract: The fibrillogenic properties of Alzheimer's Aβ peptides corresponding to residues 1–40 of the normal human sequence and to two mutant forms containing the replacement Ala21 to Gly or Glu22 to Gln were compared. At pH 7.4 and 37°C the Gln22 peptide was found to aggregate and precipitate from solution faster than the normal Aβ, whereas the Gly21 peptide aggregated much more slowly. Electron microscopy showed that the aggregates all had fibrillar structures. Circular dichroism spectra of these peptides revealed that aggregation of the normal and Gln22 sequences was associated with spectral changes consistent with a transformation from random coil to β sheet, whereas the spectrum of the Gly21 peptide remained almost unchanged during a period in which little or no aggregation occurred. When immobilised by spotting onto nitrocellulose membranes the peptides bound similar amounts of the radioisotope 65Zn2+. Of several competing metal ions, tested at 20× the concentration of Zn2+, Cu2+ displaced >95% of the radioactivity from all three peptides and Ni2+ produced >50% displacement in each case. Some other metal ions tested caused lesser displacement, but Fe2+ and Al3+ were without effect. In a saturation binding assay, a value of 3.2 µM was obtained for the binding of Zn2+ to Aβ but our data provided no evidence for a reported higher affinity site (107 nM). The results suggest that the neuropathology associated with the Gly21 mutation is not due to enhanced fibrillogenic or different metal-binding properties of the peptide and that the binding of zinc to amyloid peptides is not a specific phenomenon. 相似文献
13.
We demonstrate that complete sea urchin male pronuclear development in vitro is a two-step process involving membrane-independent chromatin decondensation and nuclear envelope-dependent pronuclear swelling. In the absence of cytoplasmic membrane vesicles (MVs), permeabilized sperm chromatin decondenses into a spherical nucleus of ≈4 μm in diameter. Pronuclear swelling to ≈7 μm requires an intact nuclear envelope, and the degree of swelling is limited by the amount of MVs assembled on the chromatin. Furthermore, after a nuclear envelope is formed, swelling can occur in the absence of additional cytoplasmic MVs. Nuclear swelling also requires ATP hydrolysis, Ca2+ and cytosolic factors, some of which are sensitive to heat and to the sulfhy-dryl alkylating agent, N-ethylmaleimide. The requirement for a nuclear envelope and the rate of pronuclear swelling are consistent with previous in vivo observations. © 1995 wiley-Liss, Inc. 相似文献
14.
Stella Erdmann Dominic Edelmann Meinhard Kieser 《Biometrical journal. Biometrische Zeitschrift》2023,65(6):2200023
The gold standard for investigating the efficacy of a new therapy is a (pragmatic) randomized controlled trial (RCT). This approach is costly, time-consuming, and not always practicable. At the same time, huge quantities of available patient-level control condition data in analyzable format of (former) RCTs or real-world data (RWD) are neglected. Therefore, alternative study designs are desirable. The design presented here consists of setting up a prediction model for determining treatment effects under the control condition for future patients. When a new treatment is intended to be tested against a control treatment, a single-arm trial for the new therapy is conducted. The treatment effect is then evaluated by comparing the outcomes of the single-arm trial against the predicted outcomes under the control condition. While there are obvious advantages of this design compared to classical RCTs (increased efficiency, lower cost, alleviating participants’ fear of being on control treatment), there are several sources of bias. Our aim is to investigate whether and how such a design—the prediction design—may be used to provide information on treatment effects by leveraging external data sources. For this purpose, we investigated under what assumptions linear prediction models could be used to predict the counterfactual of patients precisely enough to construct a test and an appropriate sample size formula for evaluating the average treatment effect in the population of a new study. A user-friendly R Shiny application (available at: https://web.imbi.uni-heidelberg.de/PredictionDesignR/ ) facilitates the application of the proposed methods, while a real-world application example illustrates them. 相似文献
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For the first time, endogenous amounts of Leu-enkephalin are measured in brain tissue with a technique preserving integrity of the entire molecular structure of the neuropeptide. Field-desorption mass spectrometry enables measurement of picomole amounts of endogenous, chemically underivatized Leu-enkephalin in canine caudate nuclei and hypothalami. The optimal sensitivity and resolution of high-performance liquid chromatography is coupled with maximal molecular specificity of field-desorption mass spectrometry to measure enkephalins in caudate nuclei and hypothalami from dog brains. This novel combination of two recent instrumental methodologies provides a firm molecular basis for calibrating the radioimmunoassay measurement of endogenous levels of biologically active brain neuropeptides. 相似文献
17.
Jerry Lee Lovelace Jozef J. Kusmierz Dominic M. Desiderio 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1991,562(1-2)
Methionine enkephalin (ME = YGGFM) was measured in five individual human post-mortem pituitaries using four different analytical methods, with the objective of comparing the molecular specificities of the methods. Radioreceptor assay (RRA) used a receptor-rich preparation from brain and [3H]etorphine as radioligand to determine ME-like receptoractivity (ME-LR). Radioimmunoassay (RIA) measured ME-like immunoreactivity (ME-LI). Pituitary samples analyzed by RRA and RIA were purified first with a high-performance liquid chromatography (HPLC) gradient on a polymer analytical column. Fast atom bombardment mass spectrometry (FAB-MS) in two different detection modes quantified ME using the protonated molecular ion MH+ of ME at 574 a.m.u. and B/E linked-field selected reaction monitoring (SRM) to monitor the specific unimolecular metastable transition that produced the unique amino acid sequence-determining tetrapeptide fragment ion YGGF+ from the MH+ precursor ion. Both FAB-MS methods used the deuterated internal standard YGG[2H5-F]M. Samples analyzed with FAB-MS were purified first with multi-dimensional reversed-phase HPLC. The first dimension was an ODS gradient, and the second dimension was a polymer isocratic elution. The following ME amounts were measured (mean ± standard error of the mean): ME-LR, 7.0 ± 1.9 μg g−1 tissue; ME-LI, 1.8 ± 0.7 μg g−1 tissue; MH+, 2.7 ± 0.6 μg g−1 tissue; SRM, 3.0 ± 0.8 μg g−1 tissue. The FAB SRM method provided the highest level of molecular specificity amount these four analytical methods used to measure picomole amounts of endogenous ME in a human pituitary. 相似文献
18.
The presence of the stud male failed to prevent implantation failure in newly inseminated females induced by administration of bromocriptine. This is in contrast with the ability of the stud male to prevent implantation failure in females induced by alien male exposure, and nutritional stress. Since bromocriptine is a potent inhibitor of hypophysial prolactin release by virtue of its stimulatory effect on hypothalamic dopaminergic activity, the results suggest that the stud male-originating luteotrophic stimulus is incapable of overriding the dopaminergic activity in bromocriptine-treated females. 相似文献
19.
Patrick Y-K Wong Kafait U. Malik Dominic M. Desiderio John C. McGiff Frank F. Sun 《Biochemical and biophysical research communications》1980,93(2):486-494
Metabolism of [9-3H]-PGI2 was studied in the isolated Tyrode's perfused rabbit liver. Five products, four radioactive and one non-radioactive, were identified in the perfusate: 19-hydroxy-6-keto-PGF1α, 6-keto-PGF1α, dinor-6-keto-PGF1α, pentanor PGF1α and a 6-keto-PGE1-like substance. The first two, 19-hydroxy-6-keto-PGF1α and 6-keto-PGF1α, represented 5% and 45% respectively, of the total radioactivity; the last two accounted for 39%. The presence of dinor and pentanor derivatives of 6-keto-PGF1α indicated that β -oxidation and oxidative-decarboxylation occurs in the liver as the major metabolic pathway of PGI2. One non-radioactive metabolite which co-migrated with authentic 6-keto-PGE1 was found to inhibit platelet aggregation, having a potency similar to authentic 6-keto-PGE1, and its effect can be eliminated by boiling and by alkali treatment. This metabolite, having similar Rf value on TLC and biological behavior as 6-keto-PGE1, may arise from oxidation of 6-keto-PGF1α via the 9-hydroxyprostaglandin dehydrogenase pathway, as suggested by recovery of tritiated water in the aqueous phase of the perfusate. This material, a potent inhibitor of platelet aggregation, may arise from PGI2 or its hydrolysis product, 6-keto-PGF1α. 相似文献
20.
Control of chromosome condensation in the sea urchin egg 总被引:3,自引:0,他引:3