全文获取类型
收费全文 | 3747篇 |
免费 | 306篇 |
出版年
2023年 | 16篇 |
2022年 | 58篇 |
2021年 | 104篇 |
2020年 | 46篇 |
2019年 | 63篇 |
2018年 | 96篇 |
2017年 | 77篇 |
2016年 | 125篇 |
2015年 | 213篇 |
2014年 | 229篇 |
2013年 | 286篇 |
2012年 | 338篇 |
2011年 | 320篇 |
2010年 | 207篇 |
2009年 | 174篇 |
2008年 | 248篇 |
2007年 | 229篇 |
2006年 | 198篇 |
2005年 | 193篇 |
2004年 | 172篇 |
2003年 | 169篇 |
2002年 | 149篇 |
2001年 | 32篇 |
2000年 | 29篇 |
1999年 | 19篇 |
1998年 | 36篇 |
1997年 | 20篇 |
1996年 | 19篇 |
1995年 | 9篇 |
1994年 | 13篇 |
1993年 | 12篇 |
1992年 | 15篇 |
1991年 | 9篇 |
1990年 | 18篇 |
1989年 | 11篇 |
1988年 | 10篇 |
1987年 | 9篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1984年 | 10篇 |
1983年 | 5篇 |
1982年 | 7篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1971年 | 3篇 |
1968年 | 10篇 |
1964年 | 2篇 |
排序方式: 共有4053条查询结果,搜索用时 558 毫秒
1.
Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus 总被引:1,自引:0,他引:1 下载免费PDF全文
Ann M. Toth Patricia Devaux Roberto Cattaneo Charles E. Samuel 《Journal of virology》2009,83(2):961-968
The measles virus (MV) accessory proteins V and C play important roles in MV replication and pathogenesis. Infection with recombinant MV lacking either V or C causes more cell death than infection with the parental vaccine-equivalent virus (MVvac), and C-deficient virus grows poorly relative to the parental virus. Here, we show that a major effector of the C phenotype is the RNA-dependent protein kinase PKR. Using human HeLa cells stably deficient in PKR as a result of RNA interference-mediated knockdown (PKRkd cells), we demonstrated that a reduction in PKR partially rescued the growth defect of C knockout (Cko) virus but had no effect on the growth of either wild-type (WT) or V knockout (Vko) virus. Increased growth of the Cko virus in PKRkd cells correlated with increased viral protein expression, while defective growth and decreased protein expression in PKR-sufficient cells correlated with increased phosphorylation of PKR and the α subunit of eukaryotic initiation factor 2. Furthermore, infection with WT, Vko, or especially Cko virus caused significantly less apoptosis in PKRkd cells than in PKR-sufficient cells. Although apoptosis induced by Cko virus infection in PKR-sufficient cells was blocked by a caspase antagonist, the growth of Cko virus was not restored to the WT level by treatment with this pharmacologic inhibitor. Taken together, these results indicate that PKR plays an important antiviral role during MV infection but that the virus growth restriction by PKR is not dependent upon the induction of apoptosis. Furthermore, the results establish that a principal function of the MV C protein is to antagonize the proapoptotic and antiviral activities of PKR. 相似文献
2.
3.
Francesca Passaretta Domenico Bosco Lucia Centurione Maria Antonietta Centurione Fabio Marongiu Roberta Di Pietro 《Journal of cellular and molecular medicine》2020,24(7):4350-4355
Human Amniotic Epithelial Cells (hAEC) isolated from term placenta are a promising source for regenerative medicine. However, it has long been debated whether the hAEC population consists of heterogeneous or homogeneous cells. In a previous study, we investigated the characteristics of hAEC isolated from four different regions of the amniotic membrane finding significant heterogeneity. The aim of this study was to evaluate the hepatic differentiation capability of hAEC isolated from these four regions. Human term placentae were collected after caesarean section and hAEC were isolated from four regions of the amniotic membrane (R1-R4, according to their relative distance from the umbilical cord) and treated in hepatic differentiation conditions for 14 days. hAEC-derived hepatocyte-like cells showed marked differences in the expression of hepatic markers: R4 showed higher levels of Albumin and Hepatocyte Nuclear Factor (HNF) 4α whereas R1 expressed higher Cytochrome P450 enzymes, both at the gene and protein level. These preliminary results suggest that hAEC isolated from R1 and R4 of the amniotic membrane are more prone to hepatic differentiation. Therefore, the use of hAEC from a specific region of the amniotic membrane should be taken into consideration as it could have an impact on the outcome of therapeutic applications. 相似文献
4.
E Sturani R Brambilla L Morello M G Cattaneo R Zippel L Alberghina 《FEBS letters》1989,255(1):191-195
PDGF consists of two polypeptide chains, A and B, and all three possible dimers have been isolated from different sources. Human PDGF, essentially AB, porcine PDGF (BB) and recombinant PDGF-AA were tested on Swiss 3T3 fibroblasts for their ability to stimulate mitogenesis, phosphoinositide turnover and tyrosine phosphorylation of the PDGF receptor. When used in saturating amounts, the three isoforms were equally active in inducing mitogenesis. However, PDGF-AA was less active than AB and BB to induce the phosphorylation of the receptor and the turnover of phosphoinositides (30% and 50%, respectively). These findings suggest that, in Swiss 3T3 fibroblasts, PDGF receptors of the alpha-type are present in a slightly lower amount than beta-type. In addition, the two types of receptor appear to have similar physiological functions. 相似文献
5.
P Beck-Peccoz A Volpi A P Maggioni M G Cattaneo G Piscitelli P Giani M Landolina G Tognoni G Faglia 《Hormones et métabolisme》1986,18(6):411-414
The effects of chronic amiodarone treatment on several thyroid and cardiac function parameters were studied in 50 euthyroid patients with refractory ventricular arrhythmias, divided in responders and nonresponders according to their sensitivity to the antiarrhythmic action of the drug. No differences in the severity of cardiac disease and blood amiodarone concentrations were found in the two groups. Amiodarone induced a significant inhibition of peripheral T4 monodeiodination, more pronounced in responders compared to nonresponders. On the contrary, only in responsive patients, elevated basal and TRH-stimulated TSH levels were observed (despite serum T3 levels were not different from those in nonresponders) and the indirect indices of cardiac performance, particularly the systolic time intervals, fell in a range usually observed in the hypothyroid states. These findings suggest that amiodarone, besides the well-known inhibition of T4 to T3 conversion, also induces a partial resistance to the thyroid hormones, which is probably involved in the therapeutical effectiveness of the drug. 相似文献
6.
RNA synthesis was followed during amino acid starvation of strains of Escherichia coli that contained both the relaxed (relA) mutation and a mutation affecting ribosome assembly that results in oversynthesis of RNA. The ribosome mutation did not by itself lead to relaxedness. The relaxed mutation could be expressed in organisms that contained the ribosome mutation. 相似文献
7.
A procedure is described that allows the determination of the surface area of aquatic plants by dipping them in a surfactant (Liquinox) dye (acridine orange) mixture and measuring the dye retained colimetrically. The method was applied to Vallisneria sp., Elodea canadensis Michx, Potamogeton richardsonii (A. Benn.) Rydb. and Myriophyllum spicatum L. For each species good relationships (0.91 < r2 < 0.99) between computed area and dye retention capacity were found. 相似文献
8.
Nicholas C. Nicolaides Fabio Palombo Kenneth W. Kinzler Bert Vogelstein Josef Jiricny 《Genomics》1996,31(3):395
Defects in mismatch repair genes cause the genetic instability characteristic of hereditary nonpolyposis colorectal cancer and a subset of sporadic colon tumors. The newest member of the mismatch repair gene family,GTBP, has recently been identified as a partial cDNA. Here, we describe the isolation of its 5′ terminus, allowing definition of the entire coding region. Several polymorphisms within the 5′ end were identified and are presented. 相似文献
9.
Gianfranco Tucci Marco Cosimo Simeone Carlo Gregori Fabio Maggini 《Plant Systematics and Evolution》1994,190(3-4):187-193
Intergenic spacers of the rRNA genes of three species of theCynareae tribe:Cynara cardunculus subsp.scolymus (artichoke),Onopordum acanthium, andO. illyricum were cloned in the plasmid pGEM-7zf(+). Detailed restriction mapping and partial sequencing of the IGSs were carried out. The structural analysis showed a clear diversity betweenCynara andOnopordum, while a high degree of homology was found between the twoOnopordum spp. In all three species a fragment of about 450 bp from the 5 end of 18S to the Acc I site with a high sequence homology was present. Nucleotide sequences upstream from the above mentioned Acc I site show a gradual decrease of homology betweenCynara andOnopordum. 相似文献
10.
Together with flow injection analysis (FIA), a chemiluminescence (CL) fiber optic biosensor system has been developed for determining glutamine in animal cell cultures. Glutaminase (GAH) and glutamate oxidase (GLO) were onto separate porous aminopropyl glass beads via glutaraldehyde activation and packed to form an enzyme column. These two enzymes acted in sequence on glutamine to produce hydrogen peroxide, which was then reacted with luminol in the presence of ferricyanide to produce a light signal. An anion exchanger was introduced on-line to eliminate interfering endogenous glutamate in view of its negative charge at pH above 3.22 (isoelectric pH). Among several resins tested, the acetate form was most effective, and this type of ion exchanger also effectively adsorbed uric acid, acetaminophen, and aspartic acid.There was an excellent linear relationship between the CL response and standard glutamine concentration in the range 1 to 100 muM. A complete analysis could be performed in 2 min, including sampling and washing with a good reproducibility (+/- 4.4%). Both the bi-enzymic and ion exchange columns were useful for at least 500 analyses when the biosensor system was applied for the glutamine determination in murine hybridoma cell cultures and insect cell cultures. The values obtained compared well with those of HPLC, thus validating the applicability of the CL fiber optic system. (c) 1993 John Wiley & Sons, Inc. 相似文献