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41.
Prolonged endoplasmic reticulum (ER) stress reduces protein synthesis and induces apoptosis in mammalian cells. When dimethyl sulfoxide (DMSO), a specific monoclonal antibody productivity (qmAb)‐enhancing reagent, is added to recombinant Chinese hamster ovary (rCHO) cell cultures (GSR cell line), it induces ER stress and apoptosis in a dose‐dependent manner. To determine an effective ER stress inhibitor, three ER stress inhibitors (BiP inducer X [BIX], tauroursodeoxycholic acid, and carbazole) are examined and BIX shows the best production performance. Coaddition of BIX (50 μm ) with DMSO extends the culture longevity and enhances qmAb. As a result, the maximum mAb concentration is significantly increased with improved galactosylation. Coaddition of BIX significantly increases the expression level of binding immunoglobulin protein (BiP) followed by increased expression of chaperones (calnexin and GRP94) and galactosyltransferase. Furthermore, the expression levels of CHOP, a well‐known ER stress marker, and cleaved caspase‐3 are significantly reduced, suggesting that BIX addition reduces ER stress‐induced cell death by relieving ER stress. The beneficial effect of BIX on mAb production is also demonstrated with another qmAb‐enhancing reagent (sodium butyrate) and a different rCHO cell line (CS13‐1.00). Taken together, BIX is an effective ER stress inhibitor that can be used to increase mAb production in rCHO cells. 相似文献
42.
Jos C. E. Serrano Juan Antonio Baena‐Fustegueras Meritxell Martin‐Gari Helene Rassendren Anna Cassanye Alba Naudí Carolina Lpez‐Cano Enric Snchez María Cruz de la Fuente‐Jurez Fernando Herrerías Gonzlez Jorge J. Olsina Kissler Albert Lecube Manuel Portero‐Otín 《Obesity (Silver Spring, Md.)》2019,27(7):1133-1140
43.
The Cbl- and ubiquitin-interacting protein T-cell ubiquitin ligand (TULA) has been demonstrated to inhibit endocytosis and downregulation of ligand-activated EGF receptor (EGFR) by impairing Cbl-induced ubiquitination. We presently report that TULA additionally inhibited clathrin-dependent endocytosis in general, as both uptake of transferrin (Tf) and low-density lipoprotein (LDL) was inhibited. Additionally, endocytosis of the raft proteins CD59 and major histocompatibility complex class I (MHC-I), which we demonstrate were mainly endocytosed clathrin-independently, but dynamin-dependently, was blocked in cells overexpressing TULA. By contrast, the uptake of ricin, which is mainly endocytosed clathrin- and dynamin-independently, was not affected by overexpressed TULA. Consistently, TULA and dynamin co-immunoprecipitated and colocalized intracellularly, and upon overexpression of dynamin the TULA-mediated inhibitory effect on endocytosis of Tf, LDL, CD59 and MHC-I was counteracted. Overexpressed dynamin did not restore ubiquitination of the EGFR, and consistently dynamin did not rescue endocytosis of the EGFR in cells overexpressing TULA. We conclude that TULA inhibits both clathrin-dependent and clathrin-independent endocytic pathways by functionally sequestering dynamin via the SH3 domain of TULA binding proline-rich sequences in dynamin. 相似文献
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Brazier Thomas Cherif Emira Martin Jean-François Gilles André Blanchet Simon Zhao Yahui Combe Marine McCairns R. J. Scott Gozlan Rodolphe E. 《Biological invasions》2022,24(8):2399-2420
Biological Invasions - Insufficient data on the origins of the first introduced propagule and the initial stages of invasion complicate the reconstruction of a species’ invasion history.... 相似文献
46.
Kristin Scoggin Rachel Lynch Jyotsana Gupta Aravindh Nagarajan Maxwell Sheffield Ahmed Elsaadi Christopher Bowden Manuchehr Aminian Amy Peterson L. Garry Adams Michael Kirby David W. Threadgill Helene L. Andrews-Polymenis 《PLoS genetics》2022,18(4)
Salmonella infections typically cause self-limiting gastroenteritis, but in some individuals these bacteria can spread systemically and cause disseminated disease. Salmonella Typhimurium (STm), which causes severe systemic disease in most inbred mice, has been used as a model for disseminated disease. To screen for new infection phenotypes across a range of host genetics, we orally infected 32 Collaborative Cross (CC) mouse strains with STm and monitored their disease progression for seven days by telemetry. Our data revealed a broad range of phenotypes across CC strains in many parameters including survival, bacterial colonization, tissue damage, complete blood counts (CBC), and serum cytokines. Eighteen CC strains survived to day 7, while fourteen susceptible strains succumbed to infection before day 7. Several CC strains had sex differences in survival and colonization. Surviving strains had lower pre-infection baseline temperatures and were less active during their daily active period. Core body temperature disruptions were detected earlier after STm infection than activity disruptions, making temperature a better detector of illness. All CC strains had STm in spleen and liver, but susceptible strains were more highly colonized. Tissue damage was weakly negatively correlated to survival. We identified loci associated with survival on Chromosomes (Chr) 1, 2, 4, 7. Polymorphisms in Ncf2 and Slc11a1, known to reduce survival in mice after STm infections, are located in the Chr 1 interval, and the Chr 7 association overlaps with a previously identified QTL peak called Ses2. We identified two new genetic regions on Chr 2 and 4 associated with susceptibility to STm infection. Our data reveal the diversity of responses to STm infection across a range of host genetics and identified new candidate regions for survival of STm infection. 相似文献
47.
Helene Bonte 《Protoplasma》1935,22(1):209-242
Ohne ZusammenfassungHerrn Privatdozent Dr. Czaja, auf dessen Veranlassung die Arbeit im Pflanzenphysiologischen Institut der Universität Berlin in Berlin-Dahlem unternommen wurde, bin ich zu herzlichem Dank für seine fördernden Ratschläge verpflichtet.Ebenso danke ich Herrn Direktor Professor Dr. Noack verbindlich für sein Interesse an der Arbeit und GewÄhrung vieler Hilfsmittel. 相似文献
48.
Swelling activation of transport pathways in erythrocytes: effects of Cl-, ionic strength, and volume changes 总被引:2,自引:0,他引:2
If swelling of acell is induced by a decrease in external medium tonicity, theregulatory response is more complex than if swelling of similarmagnitude is due to salt uptake. The present results provide anexplanation. In fish erythrocytes, two distinct transport pathways wereswelling activated: a channel of broad specificity and aK+-Clcotransporter. Each was activated by a specific signal: the channel bya decrease in intracellular ionic strength and theK+-Clcotransporter by cell enlargement. A decrease in ionic strength alsoaffectedK+-Clcotransport activity, but by acting as a negative modulator of thecotransport. Thus cells swollen by salt accumulation respond byactivating exclusively theK+-Clcotransport, leading to aCl-dependentK+ loss. By contrast, cellsswollen by electrolyte dilution respond by activating both pathways,leading to a reduced loss of electrolytes and a large loss of taurine.Thus two swelling-sensitive pathways, differently regulated, wouldallow control of the ionic composition of a cell exposed to differentvolume perturbations. 相似文献
49.
An antisense RNA regulates the bidirectional silencing property of the Kcnq1 imprinting control region
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Thakur N Tiwari VK Thomassin H Pandey RR Kanduri M Göndör A Grange T Ohlsson R Kanduri C 《Molecular and cellular biology》2004,24(18):7855-7862
The Kcnq1 imprinting control region (ICR) located in intron 10 of the Kcnq1 gene is unmethylated on the paternal chromosome and methylated on the maternal chromosome and has been implicated in the manifestation of parent-of-origin-specific expression of six neighboring genes. The unmethylated Kcnq1 ICR harbors bidirectional silencer activity and drives expression of an antisense RNA, Kcnq1ot1, which overlaps the Kcnq1 coding region. To elucidate whether the Kcnq1ot1 RNA plays a role in the bidirectional silencing activity of the Kcnq1 ICR, we have characterized factor binding sites by genomic footprinting and tested the functional consequence of various deletions of these binding sites in an episome-based system. Deletion of the elements necessary for Kcnq1ot1 promoter function resulted in the loss of silencing activity. Furthermore, interruption of Kcnq1ot1 RNA production by the insertion of a polyadenylation sequence downstream of the promoter also caused a loss of both silencing activity and methylation spreading. Thus, the antisense RNA plays a key role in the silencing function of the ICR. Double-stranded RNA (dsRNA)-mediated RNA interference is unlikely to be involved, as the ICR is active irrespective of the simultaneous production of dsRNA from the genes it silences. 相似文献
50.