全文获取类型
收费全文 | 630篇 |
免费 | 65篇 |
出版年
2021年 | 5篇 |
2020年 | 7篇 |
2019年 | 5篇 |
2018年 | 7篇 |
2017年 | 9篇 |
2016年 | 9篇 |
2015年 | 14篇 |
2014年 | 22篇 |
2013年 | 31篇 |
2012年 | 29篇 |
2011年 | 37篇 |
2010年 | 37篇 |
2009年 | 27篇 |
2008年 | 22篇 |
2007年 | 27篇 |
2006年 | 28篇 |
2005年 | 24篇 |
2004年 | 17篇 |
2003年 | 23篇 |
2002年 | 24篇 |
2001年 | 19篇 |
2000年 | 21篇 |
1999年 | 21篇 |
1998年 | 16篇 |
1997年 | 8篇 |
1996年 | 7篇 |
1995年 | 7篇 |
1994年 | 10篇 |
1993年 | 7篇 |
1992年 | 14篇 |
1991年 | 14篇 |
1990年 | 13篇 |
1989年 | 8篇 |
1988年 | 13篇 |
1986年 | 4篇 |
1985年 | 11篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 10篇 |
1981年 | 6篇 |
1979年 | 5篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1974年 | 4篇 |
1973年 | 7篇 |
1972年 | 4篇 |
1971年 | 4篇 |
1970年 | 5篇 |
1967年 | 5篇 |
1965年 | 5篇 |
排序方式: 共有695条查询结果,搜索用时 31 毫秒
591.
Low chloride stimulation of prostaglandin E2 release and cyclooxygenase-2 expression in a mouse macula densa cell line 总被引:7,自引:0,他引:7
Yang T Park JM Arend L Huang Y Topaloglu R Pasumarthy A Praetorius H Spring K Briggs JP Schnermann J 《The Journal of biological chemistry》2000,275(48):37922-37929
Reducing luminal NaCl concentration in the macula densa region of the nephron stimulates renin secretion, and this response is blocked by a specific inhibitor of cyclooxygenase-2 (COX-2) (Traynor, T. R., Smart, A., Briggs, J. P., and Schnermann, J. (1999) Am. J. Physiol. Renal Physiol. 277, F706-710). To study whether low NaCl activates COX-2 activity or expression we clonally derived a macula densa cell line (MMDD1 cells) from SV-40 transgenic mice using fluorescence-activated cell sorting of renal tubular cells labeled with segment-specific fluorescent lectins. MMDD1 cells express COX-2, bNOS, NKCC2, and ROMK, but not Tamm-Horsfall protein, and showed rapid (86)Rb(+) uptake that was inhibited by a reduction in NaCl concentration and by bumetanide or furosemide. Isosmotic exposure of MMDD1 cells to low NaCl (60 mm) caused a prompt and time-dependent stimulation of prostaglandin E(2) (PGE(2)) release that was prevented by the COX-2 specific inhibitor NS-398 (10 microm). Reducing NaCl to 60 and 6 mm for 16 h increased COX-2 expression in a chloride-dependent fashion. Low NaCl phosphorylated p38 kinase within 30 min and ERK1/2 kinases within 15 min without changing total MAP kinase levels. Low NaCl-stimulated PGE(2) release and COX-2 expression was inhibited by SB 203580 and PD 98059 (10 microm), inhibitors of p38 and ERK kinase pathways. We conclude that low chloride stimulates PGE(2) release and COX-2 expression in MMDD1 cells through activation of MAP kinases. 相似文献
592.
Effects of imperatoxin A on local sarcoplasmic reticulum Ca(2+) release in frog skeletal muscle
下载免费PDF全文
![点击此处可从《Biophysical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We have investigated the effects of imperatoxin A (IpTx(a)) on local calcium release events in permeabilized frog skeletal muscle fibers, using laser scanning confocal microscopy in linescan mode. IpTx(a) induced the appearance of Ca(2+) release events from the sarcoplasmic reticulum that are approximately 2 s and have a smaller amplitude (31 +/- 2%) than the "Ca(2+) sparks" normally seen in the absence of toxin. The frequency of occurrence of long-duration imperatoxin-induced Ca(2+) release events increased in proportion to IpTx(a) concentrations ranging from 10 nM to 50 nM. The mean duration of imperatoxin-induced events in muscle fibers was independent of toxin concentration and agreed closely with the channel open time in experiments on isolated frog ryanodine receptors (RyRs) reconstituted in planar lipid bilayer, where IpTx(a) induced opening of single Ca(2+) release channels to prolonged subconductance states. These results suggest involvement of a single molecule of IpTx(a) in the activation of a single Ca(2+) release channel to produce a long-duration event. Assuming the ratio of full conductance to subconductance to be the same in the fibers as in bilayer, the amplitude of a spark relative to the long event indicates involvement of at most four RyR Ca(2+) release channels in the production of short-duration Ca(2+) sparks. 相似文献
593.
594.
Effect of Immersion Solutions Containing Enterocin AS-48 on Listeria monocytogenes in Vegetable Foods
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Antonio Cobo Molinos Hikmate Abriouel Nabil Ben Omar Eva Valdivia Rosario Lucas Lpez Mercedes Maqueda Magdalena Martínez Caamero Antonio Glvez 《Applied microbiology》2005,71(12):7781-7787
The effect of immersion solutions containing enterocin AS-48 alone or in combination with chemical preservatives on survival and proliferation of Listeria monocytogenes CECT 4032 inoculated on fresh alfalfa sprouts, soybean sprouts, and green asparagus was tested. Immersion treatments (5 min at room temperature) with AS-48 solutions (25 μg/ml) reduced listeria counts of artificially contaminated alfalfa and soybean sprouts by approximately 2.0 to 2.4 log CFU/g compared to a control immersion treatment in distilled water. The same bacteriocin immersion treatment applied on green asparagus had a very limited effect. During storage of vegetable samples treated with immersion solutions of 12.5 and 25 μg of AS-48/ml, viable listeria counts were reduced below detection limits at days 1 to 7 for alfalfa and soybean sprouts at 6 and 15°C, as well as green asparagus at 15°C. Only a limited inhibition of listeria proliferation was detected during storage of bacteriocin-treated alfalfa sprouts and green asparagus at 22°C. Treatment with solutions containing AS-48 plus lactic acid, sodium lactate, sodium nitrite, sodium nitrate, trisodium phosphate, trisodium trimetaphosphate, sodium thiosulphate, n-propyl p-hydroxybenzoate, p-hydoxybenzoic acid methyl ester, hexadecylpyridinium chloride, peracetic acid, or sodium hypochlorite reduced viable counts of listeria below detection limits (by approximately 2.6 to 2.7 log CFU/g) upon application of the immersion treatment and/or further storage for 24 h, depending of the chemical preservative concentration. Significant increases of antimicrobial activity were also detected for AS-48 plus potassium permanganate and in some combinations with acetic acid, citric acid, sodium propionate, and potassium sorbate. 相似文献
595.
Willem J. De Lange Adrian C. Grimes Laura F. Hegge Alexander M. Spring Taylor M. Brost J. Carter Ralphe 《The Journal of general physiology》2013,142(3):241-255
Mutations in cardiac myosin binding protein C (cMyBP-C) are prevalent causes of hypertrophic cardiomyopathy (HCM). Although HCM-causing truncation mutations in cMyBP-C are well studied, the growing number of disease-related cMyBP-C missense mutations remain poorly understood. Our objective was to define the primary contractile effect and molecular disease mechanisms of the prevalent cMyBP-C E258K HCM-causing mutation in nonremodeled murine engineered cardiac tissue (mECT). Wild-type and human E258K cMyBP-C were expressed in mECT lacking endogenous mouse cMyBP-C through adenoviral-mediated gene transfer. Expression of E258K cMyBP-C did not affect cardiac cell survival and was appropriately incorporated into the cardiac sarcomere. Functionally, expression of E258K cMyBP-C caused accelerated contractile kinetics and severely compromised twitch force amplitude in mECT. Yeast two-hybrid analysis revealed that E258K cMyBP-C abolished interaction between the N terminal of cMyBP-C and myosin heavy chain sub-fragment 2 (S2). Furthermore, this mutation increased the affinity between the N terminal of cMyBP-C and actin. Assessment of phosphorylation of three serine residues in cMyBP-C showed that aberrant phosphorylation of cMyBP-C is unlikely to be responsible for altering these interactions. We show that the E258K mutation in cMyBP-C abolishes interaction between N-terminal cMyBP-C and myosin S2 by directly disrupting the cMyBP-C–S2 interface, independent of cMyBP-C phosphorylation. Similar to cMyBP-C ablation or phosphorylation, abolition of this inhibitory interaction accelerates contractile kinetics. Additionally, the E258K mutation impaired force production of mECT, which suggests that in addition to the loss of physiological function, this mutation disrupts contractility possibly by tethering the thick and thin filament or acting as an internal load. 相似文献
596.
Robert?C?Grant Wigdan?Al-Sukhni Ayelet?E?Borgida Spring?Holter Zaheer?S?Kanji Treasa?McPherson Emily?Whelan Stefano?Serra Quang?M?Trinh Vanya?Peltekova Lincoln?D?Stein John?D?McPherson Steven?Gallinger
We sequenced 11 germline exomes from five families with familial pancreatic cancer (FPC). One proband had a germline nonsense variant in ATM with somatic loss of the variant allele. Another proband had a nonsense variant in PALB2 with somatic loss of the variant allele. Both variants were absent in a relative with FPC. These findings question the causal mechanisms of ATM and PALB2 in these families and highlight challenges in identifying the causes of familial cancer syndromes using exome sequencing. 相似文献
597.
598.
Arun K. Haldar Hector A. Saka Anthony S. Piro Joe Dan Dunn Stanley C. Henry Gregory A. Taylor Eva M. Frickel Raphael H. Valdivia J?rn Coers 《PLoS pathogens》2013,9(6)
Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. Targeting of Interferon-inducible GTPases to PVs requires the formation of higher-order protein oligomers, a process negatively regulated by a subclass of IRG proteins called IRGMs. We found that the paralogous IRGM proteins Irgm1 and Irgm3 fail to robustly associate with “non-self” PVs containing either the bacterial pathogen Chlamydia trachomatis or the protozoan pathogen Toxoplasma gondii. Instead, Irgm1 and Irgm3 reside on “self” organelles including lipid droplets (LDs). Whereas IRGM-positive LDs are guarded against the stable association with other IRGs and GBPs, we demonstrate that IRGM-stripped LDs become high affinity binding substrates for IRG and GBP proteins. These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of “self” IRGM proteins from these structures. 相似文献
599.
Antonio Gálvez Rosario Lucas López Hikmate Abriouel Eva Valdivia Nabil Ben Omar 《Critical reviews in biotechnology》2013,33(2):125-152
Bacteriocins are antimicrobial peptides or proteins produced by strains of diverse bacterial species. The antimicrobial activity of this group of natural substances against foodborne pathogenic, as well as spoilage bacteria, has raised considerable interest for their application in food preservation. Application of bacteriocins may help reduce the use of chemical preservatives and/or the intensity of heat and other physical treatments, satisfying the demands of consumers for foods that are fresh tasting, ready to eat, and lightly preserved. In recent years, considerable effort has been made to develop food applications for many different bacteriocins and bacteriocinogenic strains. Depending on the raw materials, processing conditions, distribution, and consumption, the different types of foods offer a great variety of scenarios where food poisoning, pathogenic, or spoilage bacteria may proliferate. Therefore, the effectiveness of bacteriocins requires careful testing in the food systems for which they are intended to be applied against the selected target bacteria. This and other issues on application of bacteriocins in foods of dairy, meat, seafood, and vegetable origins are addressed in this review. 相似文献
600.
Guido Sonnemann Bruce Vigon Mireille Rack Sonia Valdivia 《The International Journal of Life Cycle Assessment》2013,18(5):1169-1172