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81.
Suppression of bacterial cell wall-induced polyarthritis by recombinant gamma interferon 总被引:1,自引:0,他引:1
Group A streptococcal cell wall fragments (SCW) induce erosive polyarthritis, characterized by synovial cell hyperplasia and intense mononuclear cell infiltration, in susceptible rats. Because of the known antiproliferative and immunomodulatory effects of interferon (IFN), we evaluated the effect of systemically administered alpha, beta and gamma IFN on the evolution of these destructive lesions. Treatment with gamma IFN not only reduced the acute response, but had an even greater suppressive effect on the chronic mononuclear cell-mediated destructive phase of the disease (articular index 10.2 +/- 1.2 for SCW only versus 3.8 +/- 0.7 for SCW + gamma IFN; p less than 0.01). Treatment with gamma IFN was more effective in the suppression of the arthritis than alpha, beta IFN. Histopathologic evaluation of the joints demonstrated that gamma IFN-treated animals had significantly fewer inflammatory cells, and less synovial hyperplasia and erosions than the SCW controls. gamma IFN suppression of mononuclear cell prostaglandin synthesis and synovial fibroblast proliferation was consistent with its anti-arthritic effects. These data indicate that the pathophysiology of SCW-induced erosive polyarthritis is subject to regulatory control by gamma IFN and that the mechanisms of suppression may be relevant in the treatment of rheumatoid arthritis. 相似文献
82.
Previous investigations have identified gradients of intracellular free (Ca2+)i (Ca2+i) in the cytoplasm of human fibroblasts. In this study we have compared the spatial distribution of these gradients with the subcellular distribution of cytoplasmic organelles. Using the Ca(2+)-sensitive dye fura-2 and organelle-specific fluorescent dyes, we have found that the highest Ca2+ concentrations are found in the perinuclear cytoplasm and that these regions co-localize with the Golgi apparatus. The area occupied by the endoplasmic reticulum, which includes the Golgi region plus an adjacent area, is also significantly elevated above the average cellular (Ca2+)i. Most mitochondria are located in regions different from those with the highest (Ca2+)i. A variety of phenomena which could have given rise to artifactual (Ca2+)i gradients have been ruled out, including compartmentalization of fura-2 in subcellular organelles, incomplete hydrolysis of fura-2AM esters, and the presence of pH gradients which might change the Ca2+ binding characteristics of fura-2. The existence of gradients in (Ca2+)i between ER and Golgi containing regions of the cytoplasm supports the hypothesis (Sambrook: Cell 61:197-199, 1990) that the traffic of membrane bound vesicles from ER to Golgi is directed by local variations in (Ca2+)i. 相似文献
83.
D F Mangan B Robertson S M Wahl 《Journal of immunology (Baltimore, Md. : 1950)》1992,148(6):1812-1816
Because IL-4 down-regulates several proinflammatory functions associated with human monocytes/macrophages, we explored the possibility that IL-4 also decreases monocyte survival. IL-4 caused a concentration-dependent decrease in viability of IL-1 or LPS stimulated, but not unstimulated, monocytes. Nonviable cells demonstrated classic features of programmed cell death or apoptosis, in that they were condensed and contained oligonucleosome-sized (200 bp) DNA fragments. When compared with several other cytokines commonly associated with inflammatory lesions, IL-4 was uniquely effective in enhancing cell death. We found that IL-4 enhanced death more quickly in IL-1-stimulated cells than in LPS-stimulated cells, that stimulated monocytes did not become resistant to the effects of IL-4 during culture, and that the effects of IL-4 on viability were antagonized by IFN-gamma. Enhanced cell death was stimulus-specific in that monocyte viability maintained by certain activating agents, such as Con A or CSF, was unaffected by IL-4. These findings represent the first evidence of cytokine-enhanced programmed cell death in monocytes and suggest that the antiinflammatory effects of IL-4 are mediated in part by reducing survival of stimulated monocytes in chronic lesions. 相似文献
84.
Potassium channels of fetal rat islets have been recently reported to be inadequately regulated by stimulation with glucose when compared to islets of adult rats. Though in patch clamp experiments the properties of their KATP-channels were shown to be comparable to those from adult rats, until now no closure could be demonstrated with the technique measuring the 86Rb+ efflux. Using this technique, in the presence of a basal (3 mM) glucose concentration the 86Rb+ efflux was completely insensitive to a stimulation with glucose (5.6 mM) or tolbutamide. In contrast, in islets perifused in the absence of glucose the introduction of a low glucose concentration (3 mM) or stimulation with tolbutamide alone inhibited the 86Rb+ efflux, confirming the presence of functioning KATP-channels. The absolute value of the 86Rb+ efflux rate in the absence of glucose was, however, much lower in fetal rat islets as normally observed in adult rat islets. Apart from this, the ATP content of fetal rat islets remained unchanged at either glucose concentration tested. It is suggested that in islets of fetal rats a K+ permeability is present and can be inhibited by glucose and tolbutamide but in contrast to islets of adult rats the K+ efflux is already maximally inhibited in the presence of 3 mM glucose. This may be one reason why pancreatic islets of fetal rats do not respond to glucose-stimulation with an adequate calcium uptake and insulin release. 相似文献
85.
Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. 总被引:113,自引:0,他引:113
Loss of cell cycle control and acquisition of chromosomal rearrangements such as gene amplification often occur during tumor progression, suggesting that they may be correlated. We show here that the wild-type p53 allele is lost when fibroblasts from patients with the Li-Fraumeni syndrome (LFS) are passaged in vitro. Normal and LFS cells containing wild-type p53 arrested in G1 when challenged with the uridine biosynthesis inhibitor PALA and did not undergo PALA-selected gene amplification. The converse occurred in cells lacking wild-type p53 expression. Expression of wild-type p53 in transformants of immortal and tumor cells containing mutant p53 alleles restored G1 control and reduced the frequency of gene amplification to undetectable levels. These studies reveal that p53 contributes to a metabolically regulated G1 check-point, and they provide a model for understanding how abnormal cell cycle progression leads to the genetic rearrangements involved in tumor progression. 相似文献
86.
Spirogyra insignis shows a long-term persistence of cell division synchrony in the absence of the synchronizing Zeitgeber, so that at least six generations are involved in the process. This tentatively suggests that a mechanism of transmission throughout generations of synchronizing information could maintain this synchrony. Apparently, a vital part of the molecular basis of this mechanism is a membrane proteoglycan complex. This complex could obtain temporal information from a synchronizing Zeitgeber and be transmitted to the progeny by distribution of plasma membrane between daughter cells. 相似文献
87.
Strictly anaerobic bacteria were enriched and isolated from freshwater sediment sources in the presence and absence of sulfate with sorbic acid as sole source of carbon and energy. Strain WoSo1, a Gram-negative vibrioid sulfate-reducing bacterium which was assigned to the species Desulfoarculus (formerly Desulfovibrio) baarsii oxidized sorbic acid completely to CO2 with concomitant stoichiometric reduction of sulfate to sulfide. This strain also oxidized a wide variety of fatty acids and other organic compounds. A Gram-negative rod-shaped fermenting bacterium, strain AmSo1, fermented sorbic acid stoichiometrically to about equal amounts of acetate and butyrate. At concentrations higher than 10 mM, sorbic acid fermentation led to the production of pentanone-2 and isopentanone-2 (3-methyl-2-butanone) as byproducts. Strain AmSo1 fermented also crotonate and 3-hydroxybutyrate to acetate and butyrate, and hexoses to acetate, ethanol, hydrogen, and formate. The guanine-plus-cytosine content of the DNA was 41.8±1.0 mol%. Sorbic acid at concentrations higher than 5 mM inhibited growth of this strain while strain WoSo1 tolerated sorbic acid up to 10 mM concentration. 相似文献
88.
Manuel Rey Teresa Fernández Victoria González Roberto Rodriguez 《In vitro cellular & developmental biology. Plant》1992,28(3):148-152
Summary A profitable system for the establishment of morphogenic callus cultures and indirect shoot induction and development was
accomplished from nodal shoot segments obtained from adult and micropropagated plants of kiwifruit (Actinidia deliciosa [Chev.] Liang and Ferguson, var.deliciosa) cv. “Hayward”. The effects of medium composition, cytokinin levels, dilution of salts, and type of callus derived from the
cultured primary explants were studied. Medium composition as well as type of callus greatly affected organogenic responses. 相似文献
89.
Conversion of Cellulose to Methane and Carbon Dioxide by Triculture of Acetivibrio cellulolyticus, Desulfovibrio sp., and Methanosarcina barkeri 总被引:6,自引:6,他引:0
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The fermentation of cellulose by monocultures of Acetivibrio cellulolyticus and cocultures of A. cellulolyticus-Methanosarcina barkeri, A. cellulolyticus-Desulfovibrio sp., and A. cellulolyticus-M. barkeri-Desulfovibrio sp. was studied. The monoculture produced ethanol, acetate, H2, and CO2. More acetate and less ethanol was formed by the cocultures than by the monoculture. Acetate was utilized by M. barkeri in coculture with A. cellulolyticus after a lag period, whereas ethanol was metabolized by the sulfate reducer only under conditions of low H2 partial pressure, i.e., when cocultured with A. celluloyticus-M. barkeri or when grown together with the methanogen. Only the three-component culture carried out the rapid conversion of cellulose to CO2 and methane. Furthermore, this culture hydrolyzed the most cellulose—85% of that initially present. This amount was increased to 90% by increasing the population of M. barkeri in the triculture. Methane production was also increased, and a quicker fermentation rate was achieved. 相似文献
90.
Macrophage production of fibronectin, a chemoattractant for fibroblasts 总被引:22,自引:0,他引:22
Activation of macrophages results in the production of numerous enzymes and effector molecules. One of these monokines released by macrophages can cause directed migration of connective tissue fibroblasts in vitro. Production of this macrophage-derived chemotactic factor for fibroblasts requires activation of the macrophages either in vivo or in vitro and de novo protein synthesis. The chemotactic activity in the macrophage supernatants could be removed by a fibronectin-specific affinity column and was inhibited in the presence of antibodies to fibronectin. Furthermore, chemotactic activity in the depleted macrophage supernatants could be restored by the addition of exogenous fibronectin. Fibronectin was identified in activated macrophage supernatants by an enzyme-linked immunoassay for fibronectin. From these findings it was concluded that activated macrophages release a chemoattractant for fibroblasts and that the primary chemoattractant molecule is fibronectin. The production of fibronectin by activated macrophages may thus serve as an inflammatory mediator that in addition to its other functions can recruit fibroblasts to an area of damaged tissue, where they can proliferate and form the scar tissue necessary for tissue repair. Furthermore, in chronic inflammation, the prolonged activation of macrophages may be related to the extensive fibroblast infiltration and fibrosis that can accompany these lesions. 相似文献