全文获取类型
收费全文 | 1133篇 |
免费 | 67篇 |
国内免费 | 1篇 |
专业分类
1201篇 |
出版年
2022年 | 14篇 |
2021年 | 30篇 |
2020年 | 10篇 |
2019年 | 9篇 |
2018年 | 21篇 |
2017年 | 18篇 |
2016年 | 33篇 |
2015年 | 43篇 |
2014年 | 46篇 |
2013年 | 70篇 |
2012年 | 80篇 |
2011年 | 92篇 |
2010年 | 47篇 |
2009年 | 44篇 |
2008年 | 60篇 |
2007年 | 37篇 |
2006年 | 40篇 |
2005年 | 44篇 |
2004年 | 49篇 |
2003年 | 22篇 |
2002年 | 30篇 |
2001年 | 20篇 |
2000年 | 17篇 |
1999年 | 10篇 |
1998年 | 7篇 |
1997年 | 13篇 |
1996年 | 7篇 |
1992年 | 11篇 |
1991年 | 10篇 |
1990年 | 11篇 |
1989年 | 7篇 |
1988年 | 14篇 |
1987年 | 8篇 |
1986年 | 10篇 |
1985年 | 14篇 |
1984年 | 12篇 |
1983年 | 9篇 |
1982年 | 9篇 |
1981年 | 19篇 |
1980年 | 23篇 |
1979年 | 8篇 |
1978年 | 13篇 |
1977年 | 9篇 |
1976年 | 14篇 |
1975年 | 10篇 |
1974年 | 8篇 |
1973年 | 11篇 |
1971年 | 8篇 |
1970年 | 9篇 |
1966年 | 6篇 |
排序方式: 共有1201条查询结果,搜索用时 15 毫秒
41.
1. Addition of N-ethylmaleimide to rat liver mitochondria respiring with succinate as substrate decreases both the initial rate of Ca(2+) transport and the ability of mitochondria to retain Ca(2+). As a result, Ca(2+) begins to leave the mitochondria soon after it has entered. Half-maximal effects occur at an N-ethylmaleimide concentration of about 100nmol/mg of protein. 2. The efflux of Ca(2+) induced by N-ethylmaleimide is not prevented by Mg(2+) or by Ruthenium Red at concentrations known to prevent Ca(2+) efflux when exogenous phosphate also is present. Swelling of mitochondria does not accompany N-ethylmaleimide-induced Ca(2+) efflux. 3. Addition of Ca(2+) to rat liver mitochondria in the presence of N-ethylmaleimide produces an immediate decrease in DeltaE (membrane potential), which decreases further to only a slight extent over the next 8min. Concomitant with this is an immediate increase and then levelling off of the -59DeltapH (transmembrane pH gradient). 4. Preincubation of rat liver mitochondria with p-chloromercuribenzenesulphonate, which by contrast with N-ethylmaleimide is unable to penetrate the inner mitochondrial membrane, also prevents Ca(2+) retention. The DeltaE and -59DeltapH respond to Ca(2+) addition in a manner similar to that which occurs when N-ethylmaleimide is present. Subsequent addition of mercaptoethanol produces an immediate increase in both DeltaE and -59DeltapH. At the same time Ca(2+) is rapidly accumulated by the organelles. 5. The above data are interpreted as indicating that under the conditions of Ca(2+) efflux seen here, the mitochondria retain their functional integrity. This contrasts with the uncoupling effect of Ca(2+) seen in the presence of P(i), which generally leads to a loss of mitochondrial integrity. We suggest that a unique mechanism of Ca(2+) cycling is able to take place when mitochondria have been treated with N-ethylmaleimide. 相似文献
42.
Vijaya Bharathi Srinivasan Bharat Bhushan Singh Nitesh Priyadarshi Neeraj Kumar Chauhan Govindan Rajamohan 《PloS one》2014,9(5)
Background
Multidrug resistant Klebsiella pneumoniae have caused major therapeutic problems worldwide due to the emergence of the extended-spectrum β-lactamase producing strains. Although there are >10 major facilitator super family (MFS) efflux pumps annotated in the genome sequence of the K. pneumoniae bacillus, apparently less is known about their physiological relevance.Principal Findings
Insertional inactivation of kpnGH resulting in increased susceptibility to antibiotics such as azithromycin, ceftazidime, ciprofloxacin, ertapenem, erythromycin, gentamicin, imipenem, ticarcillin, norfloxacin, polymyxin-B, piperacillin, spectinomycin, tobramycin and streptomycin, including dyes and detergents such as ethidium bromide, acriflavine, deoxycholate, sodium dodecyl sulphate, and disinfectants benzalkonium chloride, chlorhexidine and triclosan signifies the wide substrate specificity of the transporter in K. pneumoniae. Growth inactivation and direct fluorimetric efflux assays provide evidence that kpnGH mediates antimicrobial resistance by active extrusion in K. pneumoniae. The kpnGH isogenic mutant displayed decreased tolerance to cell envelope stressors emphasizing its added role in K. pneumoniae physiology.Conclusions and Significance
The MFS efflux pump KpnGH involves in crucial physiological functions besides being an intrinsic resistance determinant in K. pneumoniae. 相似文献43.
WooJin Kim Erin Zekas Robert Lodge Delia Susan-Resiga Edwidge Marcinkiewicz Rachid Essalmani Koichiro Mihara Rithwik Ramachandran Eugene Asahchop Benjamin Gelman éric A. Cohen Christopher Power Morley D. Hollenberg Nabil G. Seidah 《Molecular and cellular biology》2015,35(21):3684-3700
The proprotein convertases (PCs) furin, PC5, PACE4, and PC7 cleave secretory proteins after basic residues, including the HIV envelope glycoprotein (gp160) and Vpr. We evaluated the abundance of PC mRNAs in postmortem brains of individuals exhibiting HIV-associated neurocognitive disorder (HAND), likely driven by neuroinflammation and neurotoxic HIV proteins (e.g., envelope and Vpr). Concomitant with increased inflammation-related gene expression (interleukin-1β [IL-1β]), the mRNA levels of the above PCs are significantly increased, together with those of the proteinase-activated receptor 1 (PAR1), an inflammation-associated receptor that is cleaved by thrombin at ProArg41↓ (where the down arrow indicates the cleavage location), and potentially by PCs at Arg41XXXXArg46↓. The latter motif in PAR1, but not its R46A mutant, drives its interactions with PCs. Indeed, PAR1 upregulation leads to the inhibition of membrane-bound furin, PC5B, and PC7 and inhibits gp160 processing and HIV infectivity. Additionally, a proximity ligation assay revealed that furin and PC7 interact with PAR1. Reciprocally, increased furin expression reduces the plasma membrane abundance of PAR1 by trapping it in the trans-Golgi network. Furthermore, soluble PC5A/PACE4 can target/disarm cell surface PAR1 through cleavage at Arg46↓. PACE4/PC5A decreased calcium mobilization induced by thrombin stimulation. Our data reveal a new PC-PAR1-interaction pathway, which offsets the effects of HIV-induced neuroinflammation, viral infection, and potentially the development of HAND. 相似文献
44.
45.
46.
Arumugam Velusamy Venkatesan Manigandan Ramachandran Karthik Ramachandran Saravanan Palanisamy Satheesh Kumar Sundaresan Umamaheswari 《International journal of peptide research and therapeutics》2020,26(1):201-208
International Journal of Peptide Research and Therapeutics - Marine ecosystems are unique and a largely diverse chest of natural resources which are still to be explored for new marine species.... 相似文献
47.
Balagopalan Unni Punnee Barrera Malgorzata Muszynska-Pytel Govindan Bhaskaran Karl H. Dahm 《Archives of insect biochemistry and physiology》1993,24(4):173-185
During the last larval stage, corpora allata (CA) of Manduca sexta are inactivated by a factor from the brain. Apparently the same factor (allatinhibin, Al) is secreted by day 4 Vth instar brains kept overnight in Grace's medium. Al is rapidly inactivated by heat or acid but withstands exposure to alkali and can be recovered after freezing and lyophilization. Exposure to pronase, chymotrypsin, carboxypeptidases-A and-Y, as well as leucine aminopeptidase eliminated Al activity completely, whereas after exposure to trypsin and protease XVII-S, some residual activity remained. Inactivation by pyroglutamate aminopeptidase is interprefed as being due to prolinase activity of this enzyme. Incubation of CA with gentamicin, an aminoglycoside antibiotic, affects neither their ability to produce JH in vitro nor their viability in implantation assays. However, Al did not inactivate CA in the presence of low concentrations of gentamicin. This effect was used to guard against false positive assay results possibly produced by allatotoxic contamination. Al was purified by chromatography on Sephadex G-25. All activity recovered emerged from the columns in intermediate fractions with an apparent Mr of 1,000–2,000. © 1993 Wiley-Liss, Inc. 相似文献
48.
49.
Modified miniprep method for the rapid recovery of episomes from transfected breast epithelial cells
Episomal vectors such as pCEP4 are useful in expression cloning because they can replicate in both prokaryotes and eukaryotic cells. We have found a rapid and efficient means of extracting them from transfected MCF-10A nonmalignant human breast epithelial cells. We show that a plasmid miniprep protocol, modified by the addition of an extraction that eliminates a DNase activity, can consistently harvest pCEP4 episomes from the transfected cells (516 +/- 112 pg/harvest, mean +/- standard deviation; n = 11). The quality of the episomal DNA obtained in this manner was verified by PCR, Southern blot and the retransformation of Escherichia coli. This simple method enables the efficient recovery of episomes and is applicable in the expression cloning of potential oncogenes using host MCF-10A cells. 相似文献
50.
PknH, a transmembrane Hank's type serine/threonine kinase from Mycobacterium tuberculosis is differentially expressed under stress conditions 总被引:1,自引:0,他引:1
Sharma K Chandra H Gupta PK Pathak M Narayan A Meena LS D'Souza RC Chopra P Ramachandran S Singh Y 《FEMS microbiology letters》2004,238(1):107-113