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Ruth C. Paul B. Rainey Brian J. Sheehan Orla M. Keane Charles J. Dorman 《Current biology : CB》1999,9(24)
The relationship between environment and mutation is complex [1]. Claims of Lamarkian mutation [2] have proved unfounded [3], [4] and [5]; it is apparent, however, that the external environment can influence the generation of heritable variation, through either direct effects on DNA sequence [6] or DNA maintenance and copying mechanisms [7], [8], [9] and [10], or as a consequence of evolutionary processes [11], [12], [13], [14], [15] and [16]. The spectrum of mutational events subject to environmental influence is unknown [6] and precisely how environmental signals modulate mutation is unclear. Evidence from bacteria suggests that a transient recombination-dependent hypermutational state can be induced by starvation [5]. It is also apparent that chnages in the mutability of specific loci can be influenced by alterations in DNA topology [10] and [17]. Here we describe a remarkable instance of adaptive evolution in Salmonella which is caused by a mutation that occurs in intermediate-strength osmotic environments. We show that the mutation is not ‘directed’ and describe its genetic basis. We also present compelling evidence in support of the hypothesis that the mutational event is constrained by signals transmitted from the external environment via changes in the activity of DNA gyrase. 相似文献
3.
Popliteal-based filleted lower leg musculocutaneous free-flap coverage of a hemipelvectomy defect. 总被引:1,自引:0,他引:1
A 33-year-old man suffered from locally recurrent malignant fibrous histiocytoma of his left thigh unresponsive to previous excision, radiation therapy, chemotherapy, and hyperthermic treatment. He underwent radical hemipelvectomy for cure. Because of extensive tumor involvement, a free flap consisting of his distal left leg based on the popliteal artery was utilized to close the defect. Both the tibia and fibula were removed from their periosteal sheaths, and the foot was excised from the flap. The popliteal artery and vein were anastomosed to the iliac vessels. The flap survived, and the patient was discharged home after physical rehabilitation. We suggest that uninvolved portions of the distal leg may be utilized as a free flap to successfully close hemipelvectomy defects in selected patients when conventional pedicle flaps are unavailable. 相似文献
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Ethanol-elicited alterations in the oligomycin sensitivity and structural stability of the mitochondrial F0 . F1 ATPase 总被引:1,自引:0,他引:1
R I Montgomery W B Coleman K S Eble C C Cunningham 《The Journal of biological chemistry》1987,262(27):13285-13289
Liver mitochondria from rats fed ethanol chronically demonstrated a 35% decrease in mitochondrial ATPase activity. Moreover, the ATPase activity was inhibited only 61% by addition of oligomycin. Treatment of mitochondria from ethanol-fed rats with the detergent, Lubrol-WX, caused the release of 36% of the F1 from the resulting inner membrane particles. In comparison, only 5% of the F1 was dissociated when control mitochondria were subjected to the Lubrol treatment. However, when the units of ATPase activity from the supernatant and particles obtained after Lubrol treatment were added together, their sums were equivalent in preparations from control and ethanol-fed animals. Moreover, polyacrylamide gel electrophoresis analyses indicated equal amounts of the alpha + beta subunits of F1 in mitochondria from control and ethanol-fed rats. Reconstitution experiments with urea particles and F1 prepared from both control and ethanol mitochondria revealed a decrease in oligomycin sensitivity which could be attributed to an alteration in the functioning of either the oligomycin sensitivity conferring protein or a membrane sector subunit that interacts with oligomycin. Analysis by reconstitution also demonstrated that there were no ethanol-elicited alterations in the properties of the F1 portion of the ATP synthase complex. These observations indicate that the activity of the ATP synthase complex is altered significantly by ethanol-elicited changes in the functioning of those polypeptides involved in modulating both oligomycin sensitivity and the association of F1 with membrane sector subunits. 相似文献
8.
Modulation of thrombin-stimulated lipid responses in cultured fibroblasts. Evidence for two coupling mechanisms 总被引:3,自引:0,他引:3
Treatment of cultured fibroblasts with thrombin results in the stimulation of cell division and lipid metabolism. Proteolytically active alpha-thrombin rapidly stimulates (a) release of arachidonic acid, (b) generation of inositol phosphates, and (c) increase in cellular diacylglycerol levels. Pretreatment of the fibroblasts with chymotrypsin before alpha-thrombin prevented the first two responses, (a) and (b), and reduced response c. Treatment of fibroblasts with gamma-thrombin, a proteolytic derivative of alpha-thrombin, produced a response indistinguishable from the alpha-thrombin treatment when preceded by chymotrypsin. These data support a model, similar to one for platelets [McGowan, E. B., & Detwiler, T. C. (1986) J. Biol. Chem. 261, 739-746], that fibroblasts possess two coupling mechanisms for the stimulation of lipid metabolism by thrombin. Similar to platelets, one mechanism, R1, mediates the stimulated release of arachidonic acid and is capable of activating Ni, a GTP-binding protein. R1 is inactivated by chymotrypsin and does not respond to gamma-thrombin. The other mechanism, R2, responds to gamma-thrombin and is not activated by chymotrypsin. In contrast to the mechanisms proposed for platelets, we demonstrate that the phospholipase C responsible for the hydrolysis of phosphoinositides is not activated by R2 but is activated via R1. Importantly, stimulation of either mechanism results in the elevation of cellular diacylglycerol. This indicates that the stimulated elevation of diacylglycerol, or those events dependent upon the elevation of diacylglycerol, is not a reliable indicator for establishing the hydrolysis of phosphoinositides.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
9.
Complexes (2:1) of chymotrypsin with human alpha 2-macroglobulin have been prepared in the presence of 200 mM methylamine such that 90% of the chymotrypsin remains noncovalently bound to the alpha 2-macroglobulin. Reaction of this complex with the active-site-directed spin-labeling reagent 4-[(ethoxyfluorophosphinyl)oxy]-2,2,6,6-tetramethylpiperidinyl+ ++-1-oxy results in nitroxide labeling of the active-site serine residue of the complexed chymotrypsin. Electron spin resonance (ESR) spectra of this complex were recorded at 275 K in buffer and at 263 K in 50% glycerol. At 263 K in 50% glycerol the spectrum is that expected for a rigid glass, whereas at room temperature the ESR spectrum shows that the chymotrypsin is only slightly immobilized compared with free spin-labeled chymotrypsin. These findings are discussed in relation to possible models of inhibition of protease activity by alpha 2-macroglobulin. It is concluded that the trap mechanism of Barrett and Starkey [Barrett, A. J., & Starkey, P. M. (1973) Biochem. J. 133, 709-724] is the only model currently considered that can account for the present findings. 相似文献
10.
E J Beck D G Cunningham V W Moss J R Harris A J Pinching D J Jeffries 《BMJ (Clinical research ed.)》1987,295(6591):191-193
Trends in human immunodeficiency virus (HIV) counselling and antibody testing at a London clinic for sexually transmitted diseases showed substantial changes over a 12 month period. From around 100 a month in the summer of 1986 the numbers of people attending rose substantially to 276 in October 1986 and 475 in November at the time of the campaign in the popular press. They rose further still, to 700, at the time of AIDS (acquired immune deficiency syndrome) week in March 1987. In April they fell to the levels seen six months previously. Apart from this increase in overall numbers the proportions of women and heterosexual men who were seen increased. 相似文献