全文获取类型
收费全文 | 5240篇 |
免费 | 492篇 |
国内免费 | 1篇 |
出版年
2023年 | 23篇 |
2022年 | 66篇 |
2021年 | 132篇 |
2020年 | 66篇 |
2019年 | 96篇 |
2018年 | 107篇 |
2017年 | 78篇 |
2016年 | 154篇 |
2015年 | 243篇 |
2014年 | 260篇 |
2013年 | 313篇 |
2012年 | 404篇 |
2011年 | 377篇 |
2010年 | 220篇 |
2009年 | 192篇 |
2008年 | 235篇 |
2007年 | 233篇 |
2006年 | 198篇 |
2005年 | 219篇 |
2004年 | 194篇 |
2003年 | 192篇 |
2002年 | 177篇 |
2001年 | 105篇 |
2000年 | 115篇 |
1999年 | 97篇 |
1998年 | 49篇 |
1997年 | 51篇 |
1996年 | 33篇 |
1995年 | 34篇 |
1994年 | 34篇 |
1993年 | 34篇 |
1992年 | 75篇 |
1991年 | 69篇 |
1990年 | 63篇 |
1989年 | 69篇 |
1988年 | 48篇 |
1987年 | 43篇 |
1986年 | 51篇 |
1985年 | 40篇 |
1984年 | 33篇 |
1983年 | 40篇 |
1982年 | 30篇 |
1981年 | 38篇 |
1980年 | 24篇 |
1979年 | 37篇 |
1978年 | 46篇 |
1977年 | 28篇 |
1976年 | 26篇 |
1974年 | 28篇 |
1969年 | 22篇 |
排序方式: 共有5733条查询结果,搜索用时 281 毫秒
61.
S Abdi D N Herndon L D Traber K D Ashley J C Stothert J Maguire R Butler D L Traber 《Journal of applied physiology》1991,71(2):727-734
We investigated the contribution of the bronchial blood flow to the lung lymph flow (QL) and lung edema formation after inhalation injury in sheep (n = 18). The animals were equally divided into three groups and chronically prepared by implantation of cardiopulmonary catheters and a flow probe on the common bronchial artery. Groups 1 and 2 sheep were insufflated with 48 breaths of cotton smoke while group 3 received only room air. Just before injury, the bronchial artery of group 2 animals was occluded. The occlusion was maintained for the duration of the 24-h study period. At the end of the investigation, samples of lung were taken for determination of blood-free wet weight-to-dry weight ratio (W/D). Inhalation injury induced a sevenfold increase in QL in group 1 (7 +/- 1 to 50 +/- 9 ml/h; P less than 0.05) but only a threefold increase in group 2 (10 +/- 2 to 28 +/- 7 ml/h; P less than 0.05). The mean W/D value of group 1 animals was 23% higher than that of group 2 (5.1 +/- 0.4 vs. 3.9 +/- 0.2; P less than 0.05). Our data suggest that the bronchial circulation contributes to edema formation in the lung that is often seen after the acute lung injury with smoke inhalation. 相似文献
62.
R. H. Ashley 《The Journal of membrane biology》1989,111(2):179-189
Summary Rat brain microsomal membranes were found to contain high-affinity binding sites for the alkaloid ryanodine (k
d
3nm.B
max 0.6 pmol per mg protein). Exposure of planar lipid bilayers to microsomal membrane vesicles resulted in the incorporation, apparently by bilayer-vesicle fusion, of at least two types of ion channel. These were selective for Cl– and Ca2+, respectively. The reconstituted Ca2+ channels were functionally modified by 1 m ryanodine, which induced a nearly permanently open subconductance state. Unmodified Ca2+ channels had a slope conductance of almost 100 pS in 54mm CaHEPES and a Ca2+/TRIS+ permeability ratio of 11.0. They also conducted other divalent cations (Ba2+>Ca2+>Sr2+>Mg2+) and were markedly activated by ATP and its nonhydrolysable derivative AMPPCP (1mm). Inositol 1,4,5-trisphosphate (1–10 m) partially activated the same channels by increasing their opening rate. Brain microsomes therefore contain ryanodine-sensitive Ca2+ channels, sharing some of the characteristics of Ca2+ channels from striated but not smooth muscle sarcoplasmic reticulum. Evidence is presented to suggest they were incorporated into bilayers following the fusion of endoplasmic reticulum membrane vesicles, and their sensitivity to inositol trisphosphate may be consistent with a role in Ca2+ release from internal membrane stores. 相似文献
63.
Lu Changya David V. Gallacher Robin F. Irvine Barry V. L. Potter Ole H. Petersen 《The Journal of membrane biology》1989,109(1):85-93
Summary We have examined the effects of various inositol polyphosphates, alone and in combination, on the Ca2+-activated K+ current in internally perfused, single mouse lacrimal acinar cells. We used the patch-clamp technique for whole-cell current recording with a set-up allowing exchange of the pipette solution during individual experiments so that control and test periods could be directly compared in individual cells. Inositol 1,4,5-trisphosphate (Ins 1,4,5 P3) (10–100 m) evoked a transient increase in the Ca2+-sensitive K+ current that was independent of the presence of Ca2+ in the external solution. The transient nature of the Ins 1,4,5 P3 effect was not due to rapid metabolic breakdown, as similar responses were obtained in the presence of 5mm 2,3-diphosphoglyceric acid, that blocks the hydrolysis of Ins 1,4,5 P3, as well as with the stable analoguedl-inositol 1,4,5-trisphosphorothioate (Ins 1,4,5 P(S)3) (100 m). Ins 1,3,4 P3 (50 m) had no effect, whereas 50 m Ins 2,4,5 P3 evoked responses similar to those obtained by 10 m Ins 1,4,5 P3. A sustained increase in Ca2+-dependent K+ current was only observed when inositol 1,3,4,5-tetrakisphosphate (Ins 1,3,4,5 P4) (10 m) was added to the Ins 1,4,5 P3 (10 m)-containing solution and this effect could be terminated by removal of external Ca2+. The effect of Ins 1,3,4,5 P4 was specifically dependent on the presence of Ins 1,4,5 P3 as it was not found when 10 m concentrations of Ins 1,3,4 P3 or Ins 2,4,5 P3 were used. Ins 2,4,5 P3 (but not Ins 1,3,4 P3) at the higher concentration of 50 m did, however, support the Ins 1,3,4,5 P4-evoked sustained current activation. Ins 1,3,4 P3 could not evoke sustained responses in combination with Ins 1,4,5 P3 excluding the possibility that the action of Ins 1,3,4,5 P4 could be mediated by its breakdown product Ins 1,3,4 P3. Ins 1,3,4,5 P4 also evoked a sustained response when added to an Ins 1,4,5 P(S)3-containing solution. Ins 1,3,4,5,6 P5 (50 m) did not evoke any effect when administered on top of Ins 1,4,5 P3. In the absence of external Ca2+, addition of Ins 1,3,4,5 P4 to an Ins 1,4,5 P3-containing internal solution evoked a second transient K+ current activation. Readmitting external Ca2+ in the continued presence internally of Ins 1,4,5 P3 and Ins 1,3,4,5 P4 made the response reappear. We conclude that both Ins 1,4,5 P3 and Ins 1,3,4,5 P4 play crucial and specific roles in controlling intracellular Ca2+ homeostasis. 相似文献
64.
Isoprenoid compounds are found in all organisms. In Escherichia coli the isoprene pathway has three distinct branches: the modification of tRNA; the respiratory quinones ubiquinone and menaquinone; and the dolichols, which are long-chain alcohols involved in cell wall biosynthesis. Very little is known about procaryotic isoprene biosynthesis compared with what is known about eucaryote isoprene biosynthesis. This study approached some of the questions about isoprenoid biosynthesis and regulation in procaryotes by isolating and characterizing mutants in E. coli. Mutants were selected by determining their resistance to low levels of aminoglycoside antibiotics, which require an electron transport chain for uptake into bacterial cells. The mutants were characterized with regard to their phenotypes, map positions, enzymatic activities, and total ubiquinone content. In particular, the enzymes studied were isopentenyldiphosphate delta-isomerase (EC 5.3.3.2), farnesyldiphosphate synthetase (EC 2.5.1.1), and higher prenyl transferases. 相似文献
65.
The effects of oxidative stress on DNA damage and associated reactions, increased polyadenosine diphosphate-ribose polymerase (PARP) activity and decreased nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP) contents, have been tested in primary cultures of porcine aortic endothelial cells. The cells were treated with 50-500 microM H2O2 for 20 min or 100 microM paraquat for 3 days or were exposed to 95% O2 for 2 and 5 days. The administration of 250-500 microM H2O2 resulted in a marked increase in PARP activity and a profound depletion of ATP and NAD. Although hyperoxia had no effect on PARP activity and reduced only slightly the ATP and NAD stores, it markedly reduced the ability of endothelial cells to increase PARP activity upon exposure to DNase. Paraquat had a similar effect. Human dermal fibroblasts were also exposed to 50-500 microM H2O2 for 20 min or 95% O2 for 5 days. Their response to H2O2 differed from that of endothelial cells by their ability to maintain the ATP content at a normal level. Fibroblasts were also insensitive to the effect of hyperoxia. These results suggest that the oxidant-related DNA damage is a function of the type of oxidative stress used and may be cell-specific. 相似文献
66.
Receptor-mediated inositol 1,4,5-trisphosphate (Ins-(1,4,5)P3) generation evokes fluctuations in the cytoplasmic Ca2+ concentration ([Ca2+]i). Intracellular Ca2+ infusion into single mouse pancreatic acinar cells mimicks the effect of external acetylcholine (ACh) or internal Ins(1,4,5)P3 application by evoking repetitive Ca2+ release monitored by Ca2(+)-activated Cl- current. Intracellular infusion of the Ins(1,4,5)P3 receptor antagonist heparin fails to inhibit Ca2+ spiking caused by Ca2+ infusion, but blocks ACh- and Ins(1,4,5)P3-evoked Ca2+ oscillations. Caffeine (1 mM), a potentiator of Ca2(+)-induced Ca2+ release, evokes Ca2+ spiking during subthreshold intracellular Ca2+ infusion. These results indicate that ACh-evoked Ca2+ oscillations are due to pulses of Ca2+ release through a caffeine-sensitive channel triggered by a small steady Ins(1,4,5)P3-evoked Ca2+ flow. 相似文献
67.
J W Cary D J Petersen E T Papoutsakis G N Bennett 《Applied and environmental microbiology》1990,56(6):1576-1583
Coenzyme A (CoA)-transferase (acetoacetyl-CoA:acetate/butyrate:CoA-transferase [butyrate-acetoacetate CoA-transferase] [EC 2.8.3.9]) of Clostridium acetobutylicum ATCC 824 is an important enzyme in the metabolic shift between the acid-producing and solvent-forming states of this organism. The purification and properties of the enzyme have recently been described (D. P. Weisenborn, F. B. Rudolph, and E. T. Papoutsakis, Appl. Environ. Microbiol. 55:323-329, 1989). The genes encoding the two subunits of this enzyme have been cloned by using synthetic oligodeoxynucleotide probes designed from amino-terminal sequencing data from each subunit of the CoA-transferase. A bacteriophage lambda EMBL3 library of C. acetobutylicum DNA was prepared and screened by using these probes. Subsequent subcloning experiments established the position of the structural genes for CoA-transferase. Complementation of Escherichia coli ato mutants with the recombinant plasmid pCoAT4 (pUC19 carrying a 1.8-kilobase insert of C. acetobutylicum DNA encoding CoA-transferase activity) enabled the transformants to grow on butyrate as a sole carbon source. Despite the ability of CoA-transferase to complement the ato defect in E. coli mutants, Southern blot and Western blot (immunoblot) analyses showed that neither the C. acetobutylicum genes encoding CoA-transferase nor the enzyme itself shared any apparent homology with its E. coli counterpart. Polypeptides of Mr of the purified CoA-transferase subunits were observed by Western blot and maxicell analysis of whole-cell extracts of E. coli harboring pCoAT4. The proximity and orientation of the genes suggest that the genes encoding the two subunits of CoA-transferase may form an operon similar to that found in E. coli.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
68.
A mutation in the short 5''-proximal open reading frame on Rous sarcoma virus RNA alters virus production. 总被引:10,自引:4,他引:6
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The 5'-proximal open reading frame on Rous sarcoma virus RNA encodes a seven-amino-acid peptide and is conserved in all avian sarcoma-leukosis retroviruses. Ribosome-binding site analysis in intact chick cells showed that the 5'-proximal AUG codon is a strong site for initiation of translation in vivo. Removal of the 5'-proximal AUG codon by site-specific mutagenesis resulted in a virus with a reduced ability either to replicate or to transform a population of chicken embryo fibroblasts. These results establish a procedure for determining sites of ribosome binding and initiation of translation on mRNAs in intact eucaryotic cells and strongly suggest that the 5'-proximal open reading frame (or its AUG codon) on Rous sarcoma virus RNA has an important role in regulating viral activity. 相似文献
69.
70.
Incubation of human erythrocytes in medium containing inosine (10 mM), pyruvate (10 mM), phosphate (50 mM) and NaCl (75 mM) at pH 6.6 leads to a more than 1000-fold increase in the concentration of 5-phosphoribosyl 1-pyrophosphate (PRPP), as identified and quantified by 31P-n.m.r. spectroscopy. The accumulation is highly pH-dependent, with a maximum at extracellular pH 6.60, and the maximum value of 1.3-1.6 mmol/l of erythrocytes is attained within 1 h at 37 degrees C. PRPP was accumulated despite high concentrations of 2,3-bisphosphoglycerate (2,3-BPG), an inhibitor of PRPP synthetase. The concentration of PRPP correlated with the intracellular concentration of inorganic phosphate (Pi). Substitution of either adenosine or adenosine plus inosine for inosine in the medium did not lead to 31P-n.m.r.-detectable accumulation of PRPP. These results show that neither 2,3-BPG nor PRPP itself inhibits the synthesis of PRPP in the human erythrocyte. Adenosine, however, prevents the inosine-stimulated accumulation of PRPP. 相似文献