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11.
At inflammatory sites neutrophils are stimulated to produce a variety of toxic agents, yet rarely harm the endothelium across which they migrate. We have recently found that endothelium releases adenosine which, acting via receptors on the surface of human neutrophils, inhibits generation of toxic metabolites by stimulated neutrophils but, paradoxically, promotes chemotaxis. Agents which diminish plasma membrane viscosity affect neutrophil function similarly, possibly by modulating chemoattractant receptor number or affinity. We therefore determined whether adenosine receptor agonists modulate neutrophil function by decreasing membrane viscosity and/or chaning the affinity of chemoattractant (N-fMet-Leu-Phe, FMLP) receptors. Surprisingly, 5′-(N-ethylcar☐amido)adenosine (NECA, 10 μM), the most potent agonist at neutrophil adenosine receptors, increased plasma membrane viscosity, as measured by fluorescence anisotropy of the plasma membrane specific probe 1-(4-trimethylaminophenyl)-6-diphenyl-1,3,5-hexatriene (TMA-DPH), in unstimulated neutrophils from a mean microviscosity of 1.67 ± 0.02 (S.E.) to 1.80 ± 0.02 (p < 0.001) while inosine (10 μM), a poor adenosine receptor agonist, had no effect (1.73 ± 0.04, p =n.s. vs. control, p < 0.01 vs. NECA). Adenosine receptor agonists increased plasma membrane viscosity in neutrophils with the same order of potency previously seen for inhibition of superoxide anion generation and enhancement of chemotaxis (NECA > adenosine = N6-phenylisopropyladenosine). The adenosine receptor antagonist 8-(p-sulfophenyl)theophylline reversed the effect of NECA on plasma membrane viscosity. Unlike other agents which modulate plasma membrane viscosity, NECA (10 μM) did not significantly change the number or affinity of [3H]FMLP binding sites on neutrophils. In contrast to the hypothesis of Yuli et al. these results indicate that occupancy of adenosine receptors on neutrophils increases plasma membrane viscosity without affecting chemoattractant receptor display. 相似文献
12.
Günter Kämper Hans-Ulrich Kleindienst 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1990,167(2):193-200
1. | Filiform hairs of various lengths on the cerci of adult crickets vibrate in a sound field. These movements were measured with a photodetector for sound frequencies from 10 Hz to 200 Hz in the species Acheta domestica, Gryllus bimaculatus and Phaeophilacris spectrum. |
2. | With low air-particle velocities, the hair shafts were deflected sinusoidally from their resting position, without bending or secondary oscillations (Figs. 2 A, 3 A). At higher velocities (from ca. 80 mm/s peak velocity, depending on the properties of the individual hairs), the shaft struck the cuticular rim of the socket in which the base of the hair is seated (Fig. 2B). This contact was made at an average angular displacement from the resting position of 5.16°±1.0°. |
3. | The best frequencies of the hairs were found to be between 40 Hz and 100 Hz (Fig. 5A). The slope of the amplitude curve for constant peak air-particle velocity at frequencies below the best frequencies was between 0 and 6 dB/octave. Long hairs had smaller slope values than short hairs (Fig. 5C). |
4. | At its best frequency the ratio of maximal tip displacement of a hair to the displacement of the air particles in the sound field was between 0.2 and 2. Only a small number of hairs (2 out of 36) showed tip displacements exceeding twice the air-particle displacement. The values of maximal angular displacement were not correlated to hair length (Fig. 5 B). |
5. | The angular displacement of the hairs was phase shifted with respect to the air-particle velocity by 0° to +45° (phase lead) at sound frequencies around 10 Hz and by -45° to -120° (phase lag) at 200 Hz (Figs. 3C, 4B). At a particular frequency long hairs tended to have larger phase lags than shorter hairs (Fig. 5D). |
13.
Nicotinic Agonists Regulate α-Bungarotoxin Binding Sites of TE671 Human Medulloblastoma Cells 总被引:1,自引:1,他引:0
The TE671 human medulloblastoma cell line expresses a variety of characteristics of human neurons. Among these characteristics is the expression of membrane-bound high-affinity binding sites for alpha-bungarotoxin, which is a potent antagonist of functional nicotinic acetylcholine receptors on these cells. These toxin binding sites represent a class of nicotinic receptor isotypes present in mammalian brain. Treatment of TE671 cells during proliferative growth phase with nicotine or carbamylcholine, but not with muscarine or d-tubocurarine, induced up to a five-fold increase in the density of radiolabeled toxin binding sites in crude membrane fractions. This effect was blocked by co-incubation with the nicotinic antagonists d-tubocurarine and decamethonium, but not by mecamylamine or by muscarinic antagonists. Following a 10-13 h lag phase upon removal of agonist, recovery of the up-regulated sites to control values occurred within an additional 10-20 h. These studies indicate that the expression of functional nicotinic acetylcholine receptors on TE671 cells is subject to regulation by nicotinic agonists. Studies of the murine CNS have consistently indicated nicotine-induced up-regulation of nicotinic acetylcholine receptors, thereby supporting the identification of the toxin binding site on these cells as the functional nicotinic receptor. Although a mechanism for this effect is not apparent, nicotine-induced receptor blockade does not appear to be involved. 相似文献
14.
Richard C. Woodman John T. Curnutte Bernard M. Babior 《Free radical biology & medicine》1988,5(5-6):355-361
We examined the effects of the recombinant human colony stimulating factors GM-CSF and G-CSF, cycloheximide (a protein synthesis inhibitor) and dihydrocytochalasin B (a microfilament disrupting agent) upon FMLP (N-formyl-methionyl-leucylphenylalanine)-stimulated O2 − production by neutrophils. We confirmed a time dependent augmentation of O2 − production following preincubation of neutrophils either alone or with colony stimulating factors. Furthermore, we found that GM-CSF, but not G-CSF, increased O2 − production at some concentrations of the stimulus. Preincubation of neutrophils with cycloheximide in the absence of CSF caused a marked fall in O2−-production that was first evident at 2 hours. The fall in O2−-forming capacity caused by cycloheximide was much less pronounced if dihydrocytochalasin B was also included in the preincubation buffer. These findings suggest a previously unrecognized role for de novo protein synthesis in maintaining the ability of neutrophils to manufacture O2−, and support earlier studies indicating that the cycling of FMLP receptors between the cell membrane and an intracellular compartment is important in determining the magnitude of the respiratory burst in FMLP-stimulated neutrophils. 相似文献
15.
Adriaan P. de Bruïne Winand N. M. Dinjens Margriet M. J. Pijls Edith P. M. v. d. Linden Mat J. M. Rousch Peter T. Moerkerk Antony F. P. M. de Goeij Fred T. Bosnian 《Virchows Archiv. B, Cell pathology including molecular pathology》1992,62(1):311-320
In colonic neoplasms, endocrine differentiation is encountered not only in carcinoid tumors but also in adenocarcinomas, where
endocrine cells may represent a distinct line of differentiation in the tumor. The significance of endocrine differentiation
in colorectal cancer is not well established, partly because of the paucity of tumor cell lines which can serve as a model
for studying endocrine differentiation. In this report we describe the properties of NCI-H716 cells, a cell line derived from
a poorly differentiated adenocarcinoma of the caecum, under various in vitro conditions and as xenografts in athymic mice.
Phenotypical properties were immunohistochemically assessed using a panel of differentiation related antibodies, and also
by Northern blot analysis and by electron microscopy. Receptors for biogenic amines and peptide hormones were analyzed by
ligand binding assay. These studies show that:
相似文献
1. | NCI-H716 cells can be undifferentiated, or show endocrine, mucin-producing or “amphicrine” properties. |
2. | Endocrine differentiation of NCI-H716 cells preferentially occurs in xenografts in athymic mice, which suggests that mesenchymal elements induce endocrine differentiation. |
3. | NCI-H716 cells express large amounts of high affinity receptors for gastrin, serotonin and somatostatin and these substances can regulate growth. Thus, NCI-H716 cells form a suitable model for the study of endocrine differentiation in intestinal epithelium and of auto- or paracrine growth regulation in intestinal neoplasia. |
16.
Identification and characterization of a pregnane steroid recognition site that is functionally coupled to an expressed GABAA receptor 总被引:2,自引:0,他引:2
Conclusion Based on the pharmacological and biochemical evidence to date, especially that derived from the recombinantly expressed receptor studies, the suggestion that a novel GBRC-linked steroid recognition site exists becomes a cogent argument. The high affinity of the steroid site for certain naturally occurring metabolites of progesterone and glucocorticoids favors a physiologic role for these steroids in the regulation of brain excitability. Clearly, investigations of such a regulatory role is warranted. If present, it provides an important example of endocrine control of a major inhibitory neurotransmitter in the CNS. Moreover, as we gain a greater understanding of the molecular organization of the GBRC, the putative steroid site provides a novel target for the rational design of therapeutic agents for the treatment of anxiety, epilepsy, and insomnia.Special issue dedicated to Dr. Eugene Roberts. 相似文献
17.
Christine No Jordi Hernandez-Borrell Stephen C. Kinsky Eiji Matsuura Lee Leserman 《生物化学与生物物理学报:生物膜》1988,946(2)
We have prepared liposomes containing methotrexate-γ-dimyristoylphosphatidylethanolamine (MTX-DMPE liposomes), to which protein A was covalently coupled, permitting specific association of these liposomes in vitro with murine cells preincubated with relevant protein A-binding monoclonal antibodies. In the absence of antibody the presence of externally-oriented methotrexate (MTX) in MTX-DMPE liposomes did not result in greater binding to cells than liposomes made without MTX-γ-DMPE. Derivation of methotrexate with phospholipid permits enhanced drug-liposome association. These liposomes are more resistant than conventional liposomes to repeated cycles of freezing and thawing. MTX-DMPE liposomes are comparable to antibody-targeted liposomes made with encapsulated water-soluble methotrexate both with respect to specific binding to target cells and drug effect. The inhibitory effects off MTX-liposomes, as well as free MTX, were reversible by either thiamin pyrophosphate (Tpp) or N5-formyltetrahydrofolate (F-THF), while the effects of MTX-DMPE liposomes were reversed only by N5-formyltetrahydrofolate. This suggests that the toxicity of non-targeted MTX-liposomes may be due to leakage of the encapsulated MTX. The absence of an effect of thiamin pyrophosphate on non-targeted MTX-DMPE liposomes indicates that they do not enter into the cell via the normal folate transport system. 相似文献
18.
W. Conrad Liles Stephen Taylor Richard Finnell Henry Lai Neil M. Nathanson 《Journal of neurochemistry》1986,46(3):977-982
The tottering mouse (tg/tg) is a single-locus mutant, phenotypically characterized by the development of epilepsy associated with distinct electroencephalographic abnormalities. Because of reported alterations in muscarinic receptor (mAChR) number in various seizure states, mAChR density was examined in discrete brain regions of tottering (tg/tg) and coisogenic wild-type (+/+) mice. Saturation binding experiments revealed a widespread decrease in membrane mAChR density in the CNS of adult tottering (tg/tg) mice as compared with age-matched control wild-type (+/+) mice. The decrease was most pronounced in the hippocampus, where tg/tg mice exhibited a 40-60% reduction in mAChR density with no change in the affinity of the receptor for antagonists or agonists. At postnatal day 10, before the reported onset of electroencephalographic abnormalities, 114 and 65% increases in mAChR density were observed in the tg/tg hippocampus and cortex, respectively. Following the development of seizure activity at postnatal day 22, mAChR density in the tg/tg hippocampus was reduced by 29%. No change in brain mAChR density was seen in adult heterozygotes (+/tg), which do not develop electroencephalographic or seizure abnormalities. These results indicate that the development of reduced mAChR number in the CNS of the tg/tg mouse is secondary to abnormal neuronal activity, providing further support for the hypothesis that membrane depolarization can cause a decrease in neuronal mAChR density. 相似文献
19.
Cholinergic- and Adrenergic-Stimulated Inositide Hydrolysis in Brain: Interaction, Regional Distribution, and Coupling Mechanisms 总被引:16,自引:14,他引:2
Carbachol and norepinephrine were used as agonists to compare and contrast cholinergic and adrenergic stimulation of inositide breakdown in rat brain slices. Carbachol acts through a muscarinic (possibly M1) receptor and norepinephrine acts through an alpha 1 adrenoceptor. Studies in cerebral cortical slices indicated that both agonists stimulated the production of inositol-1-phosphate and glycerophosphoinositol. Although the initial rates for the stimulation of inositol phosphate release were similar for the two ligands, the response to norepinephrine continued for 60 min and was larger compared with carbachol which plateaued at 30 min. The presence of carbachol did not affect the ED50 for norepinephrine. Concentrations of carbachol near the ED50 in combination with norepinephrine resulted in an additive response whereas maximal concentrations of carbachol and norepinephrine resulted in a less than additive response in the cortex. This negative interaction was also seen in the hippocampus and hypothalamus but not in the striatum, brainstem, spinal cord, olfactory bulb, or cerebellum. Norepinephrine had a larger response than carbachol in the hippocampus, striatum, and spinal cord, but the reverse was true in the olfactory bulb. Manganese (1 mM) stimulated the incorporation of [3H]inositol into phosphatidylinositol (PtdIns) four- to fivefold but not into polyphosphoinositides. The stimulation by manganese of PtdIns labelling increased the nonstimulated release of inositol phosphates but did not affect the stimulated release of inositol phosphates by carbachol or norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
20.
The Scatchard plot in a radioreceptor assay depends upon the definition of specific binding and the quality of the iodinated
hormone used. Iodination of protein hormones may alter it so that it no longer binds to the receptor and methods are available
to measure the extent of this inactivation. When appropriate corrections are made for specific binding and the amount of inactive
iodinated hormone in an assay, both qualitative and quantitative differences were observed in estimates of binding capacity
and affinity in some well characterised hormone receptor systems.
Theoretical predictions derived from Scatchard analysis of irreversible unimolecular hormone-receptor interactions were applicable,
both qualitatively and quantitatively to two irreversible hormone-receptor systems. A method described permits a more accurate
estimate of capacity from radioreceptor assay data. 相似文献