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11.
Barbara J. Wilcox Eric S. Corp Daniel M. Dorsa Dianne P. Figlewicz M. R. C. Greenwood Stephen C. Woods Denis G. Baskin 《Peptides》1989,10(6):1159-1164
Recent reports have suggested that the obesity and hyperphagia of the genetically obese Zucker rat may be related to defective insulin action or binding in the hypothalamus. We used quantitative autoradiography to determine if insulin binding is altered in specific hypothalamic nuclei associated with food intake. Insulin binding was measured in the arcuate (ARC), dorsomedial (DMN), and ventromedial (VMN) hypothalamic nuclei of 3–4-month-old lean (Fa/Fa) and genetically obese (fa/fa) Zucker rats. A consistently reproducible 15% increase in the total specific binding of 0.1 nM [125I]-insulin was found in the ARC of the obese genotype. A slight increase in insulin binding in the DMN was also found. No difference in specific insulin binding was found between genotypes in the VMN. Nonlinear least squares analysis of competitive binding studies showed that the Kd of the ARC insulin binding site was 33% higher in the lean rats than in the obese rats, indicating an increased affinity for insulin. No difference in site number (Bmax) was found in the ARC, DMN or VMN, and no evidence was found for reduced insulin binding in the hypothalamus of the obese (fa/fa) genotype. The results suggest that hyperphagia and obesity of the obese (fa/fa) Zucker rat genotype may be associated with increased insulin binding in the arcuate nucleus. 相似文献
12.
The effect of TPA (12-O-tetradecanoylphorbol-13-acetate) upon ionic exchanges was investigated in eggs of the sea urchin Arbacia lixula. Ouabain-sensitive 86Rb uptake and amiloride-sensitive 24Na influx were dramatically stimulated after TPA addition, indicating an enhancement of total ionic permeabilities. Stimulation by TPA of both Na+/H+ and Na+/K+ exchanges was canceled by amiloride, suggesting that activation of protein kinase C elicits, via Na+/H+ activity, stimulation of the sodium pump. However, TPA did not stimulate sodium pump activity and Na+/H+ exchange at the same rate as fertilization, probably because of an absence of calcium-dependent events. Further fertilization of TPA-pretreated eggs triggered an enhancement of sodium pump activity when the TPA treatment duration did not exceed 10 min. It is suggested that TPA activates preexisting transporting mechanisms in plasma membranes of unfertilized eggs (Na+ pump, Na+/H+ exchange) without eliciting corresponding regulatory mechanisms (Na+ stat, pH stat). 相似文献
13.
M Denis A Wilhelmsson S Cuthill L Poellinger J A Gustafsson 《Biochemical and biophysical research communications》1989,163(1):444-451
The rat hepatic glucocorticoid, dioxin and oxysterol receptors were subjected to high performance liquid chromatography on size-exclusion and anion-exchange columns. Both the glucocorticoid receptor and the dioxin receptor had a Stokes radius Rs approximately 7.5 nm, expected value for heteromeric complexes containing a dimer of the Mr approximately 90,000 heat shock protein, hsp90 (Rs approximately 7.0 nm). The oxysterol receptor represented a much smaller entity (Rs approximately 6.0 nm). When analyzed on a Mono Q anion-exchange column, the molybdate-stabilized glucocorticoid receptor and dioxin receptor eluted as single peaks at approximately 0.30 M and 0.26-0.28 M NaCl, respectively, whereas the oxysterol receptor represented a less negatively charged species (0.11-0.14 M NaCl). Following washing of the Mono Q column with molybdate-free buffer, the activated monomeric glucocorticoid receptor was detected (0.10-0.12 M NaCl). In contrast, no modification in the elution pattern of the dioxin receptor and the oxysterol receptor was observed. These data demonstrate differences in the physico-chemical properties of the glucocorticoid, dioxin and oxysterol receptors, respectively, which might reflect structural differences. 相似文献
14.
N Boujrad I Denis V Papadopoulos C Pisselet P Bouchard M A Drosdowsky M T Hochereau de Reviers S Carreau 《Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie》1990,310(9):417-421
In mature rat Leydig cells, the testosterone output (24 ng/10(6) Leydig cells/4hrs.) is increased 10 fold by LH; the addition of serum from either control or castrated or hypophysectomized rams inhibits (60%) the LH-stimulated testosterone production. Similarly, the incubation of immature rat Leydig cells with sera from hypophysectomized patients leads to a diminution (70 and 30% respectively) of both basal (0.98 ng) and LH stimulated (3.44 ng) testosterone biosynthesis. These data suggest the existence of an LH inhibitor (or inhibitors) in blood from ram and human; in addition, this substance is not only of testicular origin and is not an LH-related molecule. 相似文献
15.
The HOX-5 and surfeit gene clusters are linked in the proximal portion of mouse chromosome 2 总被引:1,自引:0,他引:1
Lisa Stubbs Clare Huxley Brigid Hogan Timothy Evans Mike Fried Denis Duboule Hans Lehrach 《Genomics》1990,6(4)
Using an interspecies backcross, we have mapped the HOX-5 and surfeit (surf) gene clusters within the proximal portion of mouse chromosome 2. While the HOX-5 cluster of homeobox-containing genes has been localized to chromosome 2, bands C3-E1, by in situ hybridization, its more precise position relative to the genes and cloned markers of chromosome 2 was not known. Surfeit, a tight cluster of at least six highly conserved “housekeeping” genes, has not been previously mapped in mouse, but has been localized to human chromosome 9q, a region of the human genome with strong homology to proximal mouse chromosome 2. The data presented here place HOX-5 in the vicinity of the closely linked set of developmental mutations rachiterata, lethargic, and fidget and place surf close to the proto-oncogene Abl, near the centromere of chromosome 2. 相似文献
16.
C. Denis D. Dormois J. Castells R. Bonnefoy S. Padilla A. Geyssant J. R. Lacour 《European journal of applied physiology and occupational physiology》1988,57(4):474-481
To compare the results obtained by incremental or constant work load exercises in the evaluation of endurance conditioning, a 20-week training programme was performed by 9 healthy human subjects on the bicycle ergometer for 1 h a day, 4 days a week, at 70-80% VO2max. Before and at the end of the training programme, (1) the blood lactate response to a progressive incremental exercise (18 W increments every 2nd min until exhaustion) was used to determine the aerobic and anaerobic thresholds (AeT and AnT respectively). On a different day, (2) blood lactate concentrations were measured during two sessions of constant work load exercises of 20 min duration corresponding to the relative intensities of AeT (1st session) and AnT (2nd session) levels obtained before training. A muscle biopsy was obtained from vastus lateralis at the end of these sessions to determine muscle lactate. AeT and AnT, when expressed as % VO2max, increased with training by 17% (p less than 0.01) and 9% (p less than 0.05) respectively. Constant workload exercise performed at AeT intensity was linked before training (60% VO2max) to a blood lactate steady state (4.8 +/- 1.4 mmol.l-1) whereas, after training, AeT intensity (73% VO2max) led to a blood lactate accumulation of up to 6.6 +/- 1.7 mmol.l-1 without significant modification of muscle lactate (7.6 +/- 3.1 and 8.2 +/- 2.8 mmol.kg-1 wet weight respectively). It is concluded that increase in AeT with training may reflect transient changes linked to lower early blood lactate accumulation during incremental exercise.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
17.
Robert Cedergren B. Franz Lang Denis Gravel 《Origins of life and evolution of the biosphere》1988,18(3):299-305
Proposals that an RNA-based genetic system preceeded DNA, stem from the ability of RNA to store genetic information and to promote simple catalysis. However, to be a valid basis for the RNA world, RNA catalysis must demonstrate or be related to intrinsic chemical properties which could have existed in primordial times. We analyze this question by first classifying RNA catalysis and related processes according to their mechanism. We define: (A) thedisjunct nucleophile class which leads to 5-phosphates. These include Group I and II intron splicing, nuclear mRNA splicing and RNase P reactions. Although Group I introns and its excision mechanism is likely to have existed in primordial times, present-day examples have arisen independently in different phyla much more recently. Comparative methodology indicates that RNase P catalysis originated before the divergence of the major kingdoms. In addition, alldisjunct nucleophile reactions can be interrelated by a proposed mechanism involving a distant 2-OH nucleophile. (B) theconjunct nucleophile class leading to 3-phosphates. This class is composed of self-cleaving RNAs found in plant viruses and the newt. We propose that tRNA splicing is related to this mechanism rather than the previous one. The presence of introns in tRNA genes of eukaryotes and archaebacteria supports the idea that tRNA splicing predates the divergence of these cell types. 相似文献
18.
Pulmonary alveoler macrophages exposedto very short chrysotile asbestos fibers present a typical cytotoxic response: extracellular releases of lactate dehydrogenase and -galactosidase, and a decrease in cellular ATP content. The objective of this study was to determine if nicotinamide and 3-aminobenzamide, two inhibitors of the ADP-ribosyl transferase, could modify the in vitro toxicity of chrysotilee fibers. After 30 min of pre-exposure with each of the two inihibitors, pulmonary alveolar macrophage monolayers were concominantly exposed for 18 hours to 50g of fibers. It was observed that, in a dose-effect relationship (5 to 30 mM), nicotinamide was very effective in reducing the extracellular liberation of the marker enzymes. At 30 mM, the enzyme releases in the medium had returned to control values; the restoration of cell viability was confirmed by ATP levels. Up to 5 mM 3-aminobenzamide did not provide any protection against chrysotile cytotoxicity. Nicotinic acid, a structural analogue of nicotinamide, but not an inhibitor of the ADP-ribosyl transferase, also showed no protective effect. Nicotinamide and 3-aminobenzamide increased the intracellular NAD+ pools, respectively by 350% and 250%. However, with or without additives, the chrysotile fibers caused a constant and significant decrease in NAD+ levels (40–55 pmoles). These results suggest that the inhibition of the nuclear ADP-ribosyl transferase is not the major mechanism by which nicotinamide protects pulmonary alveolar macrophages against the chrysotile asbestos fibers.Abbreviations 3-AB
3-aminobenzamide
- ADPRT
ADP-ribosyl transferase
- -GAL
-galactosidase
- DTT
dithiothreitol
- FBS
fetal bovine serum
- FMN
flavin mononucleotide
- HEPES
N-2-hydroxyethyl piperazine-N-2-ethanesulfonic acid
- LDH
lactate dehydrogenase
- NAD+
nicotinamide adenine dinucleotide (oxidized form)
- NADH
nicotimide adenine dinucleotide (reduced forms)
- NADPH
nicotimide adenine dinucleotide phosphate (reduced form)
- NAM
nicotinamide
- NIC
nicotinic acid
- ORS
oxygen radical species
- PAM
pulmonary alveolar macrophages
- S.E.
standard error of the mean
- TAPS
tris (hydroxymethyl) methylamino-propane sulfonic acid
- TRIS
tris (hydroxymethyl) aminomethane
- VSF
very short chrysotile fibers 相似文献
19.
20.
Denis A. Magoffin Gregory F. Erickson 《In vitro cellular & developmental biology. Plant》1988,24(9):862-870
Summary Although luteinizing hormone (LH) alone stimulates ovarian interstitial cells cultured in serum-free medium to synthesize
large amounts of androgens, there seem to be additional factors in vivo that modulate the time course and magnitude of the
cellular responses to LH. In an attempt to develop a more nearly physiologic cell culture model, lipoproteins, insulin, and
insulinlike growth factor-I (IGF-I) were added to the serum-free medium. The effects of these modifications on androgen biosynthesis
by dispersed cells from ovaries of hypophysectomized immature rats cultured in 96-well tissue culture plates were examined.
A saturating dose of LH stimulated a 25-fold increase in androsterone synthesis at 2 d, which decreased at 4 and 6 d. Addition
of human high density (hHDL) or human low density lipoprotein (hLDL) caused a 2.5-fold increase in LH-stimulated androsterone
synthesis. Cells were approximately twice as sensitive to hHDL (ED50=5.5±0.5 μg cholesterol/ml) compared to hLDL (ED50=9.1±1.1 μg cholesterol/ml). Surprisingly, rat HDL caused only a 40% increase in LH-stimulated androsterone synthesis. When
insulin alone was added to cells cultured with a saturating dose of LH, there was a 2.8-fold increase in androsterone synthesis.
Addition of hHDL and insulin together caused a synergistic increase in LH-stimulated androsterone synthesis. In contrast to
hHDL, which did not change the time course of LH-stimulated androsterone production, insulin prolonged maximal LH-stimulated
androsterone synthesis at 4 and 6 d. Inasmuch as the ED50 for insulin action (1.3±0.1 μg/ml) was supraphysiologic, the effects of IGF-I on LH-stimulated androgen synthesis were examined.
IGF-I mimicked all of the effects of insulin, but at a physiologic concentration (ED50=2.5±0.3 ng/ml). Ovarian cells cultured in serum-free medium supplemented with hHDL and insulin or IGF-I exhibit responses
that closely approximate the physiologic responses observed in vivo. These results suggest that lipoproteins and IGF-I are
important physiologic stimulators of ovarian theca-interstitial cell androgen biosynthesis which, when added to the serum-free
medium, make the cellular responses in this in vitro model more nearly approximate the responses in vivo.
This research was supported by research center grant HD 12303 from the National Institute of Child Health and Human Development,
Bethesda, MD, and USCD Academic Senate grant RM-169M 相似文献