全文获取类型
收费全文 | 25448篇 |
免费 | 1379篇 |
国内免费 | 1024篇 |
出版年
2023年 | 425篇 |
2022年 | 567篇 |
2021年 | 687篇 |
2020年 | 651篇 |
2019年 | 892篇 |
2018年 | 860篇 |
2017年 | 577篇 |
2016年 | 564篇 |
2015年 | 706篇 |
2014年 | 1557篇 |
2013年 | 1957篇 |
2012年 | 1079篇 |
2011年 | 1463篇 |
2010年 | 1082篇 |
2009年 | 1177篇 |
2008年 | 1186篇 |
2007年 | 1284篇 |
2006年 | 1097篇 |
2005年 | 989篇 |
2004年 | 914篇 |
2003年 | 744篇 |
2002年 | 637篇 |
2001年 | 437篇 |
2000年 | 385篇 |
1999年 | 394篇 |
1998年 | 346篇 |
1997年 | 321篇 |
1996年 | 331篇 |
1995年 | 312篇 |
1994年 | 282篇 |
1993年 | 243篇 |
1992年 | 243篇 |
1991年 | 244篇 |
1990年 | 157篇 |
1989年 | 172篇 |
1988年 | 142篇 |
1987年 | 120篇 |
1986年 | 97篇 |
1985年 | 231篇 |
1984年 | 331篇 |
1983年 | 233篇 |
1982年 | 272篇 |
1981年 | 225篇 |
1980年 | 226篇 |
1979年 | 186篇 |
1978年 | 155篇 |
1977年 | 159篇 |
1976年 | 161篇 |
1975年 | 124篇 |
1974年 | 99篇 |
排序方式: 共有10000条查询结果,搜索用时 160 毫秒
1.
Suzanne Camus Sergio Menéndez Kenneth Fernandes Nelly Kua Geng Liu Dimitris P. Xirodimas David P. Lane Jean-Christophe Bourdon 《Cell cycle (Georgetown, Tex.)》2012,11(8):1646-1655
The discovery that the single p53 gene encodes several different p53 protein isoforms has initiated a flurry of research into the function and regulation of these novel p53 proteins. Full-length p53 protein level is primarily regulated by the E3-ligase Mdm2, which promotes p53 ubiquitination and degradation. Here, we report that all of the novel p53 isoforms are ubiquitinated and degraded to varying degrees in an Mdm2-dependent and -independent manner, and that high-risk human papillomavirus can degrade some but not all of the novel isoforms, demonstrating that full-length p53 and the p53 isoforms are differentially regulated. In addition, we provide the first evidence that Mdm2 promotes the NEDDylation of p53β. Altogether, our data indicates that Mdm2 can distinguish between the p53 isoforms and modify them differently. 相似文献
2.
Binding of the cationic tetra(tributylammoniomethyl)-substituted hydroxoaluminum phthalocyanine (AlPcN4) to bilayer lipid membranes was studied by fluorescence correlation spectroscopy (FCS) and intramembrane field compensation (IFC) methods. With neutral phosphatidylcholine membranes, AlPcN4 appeared to bind more effectively than the negatively charged tetrasulfonated aluminum phthalocyanine (AlPcS4), which was attributed to the enhancement of the coordination interaction of aluminum with the phosphate moiety of phosphatidylcholine by the electric field created by positively charged groups of AlPcN4. The inhibitory effect of fluoride ions on the membrane binding of both AlPcN4 and AlPcS4 supported the essential role of aluminum-phosphate coordination in the interaction of these phthalocyanines with phospholipids. The presence of negative or positive charges on the surface of lipid membranes modulated the binding of AlPcN4 and AlPcS4 in accord with the character (attraction or repulsion) of the electrostatic interaction, thus showing the significant contribution of the latter to the phthalocyanine adsorption on lipid bilayers. The data on the photodynamic activity of AlPcN4 and AlPcS4 as measured by sensitized photoinactivation of gramicidin channels in bilayer lipid membranes correlated well with the binding data obtained by FCS and IFC techniques. The reduced photodynamic activity of AlPcN4 with neutral membranes violating this correlation was attributed to the concentration quenching of singlet excited states as proved by the data on the AlPcN4 fluorescence quenching. 相似文献
3.
《Cell reports》2020,30(1):112-123.e4
- Download : Download high-res image (131KB)
- Download : Download full-size image
4.
The linkage of the Phi, Pgd, Po2, S, H and halothane sensitivity loci was followed in a Belgian Landrace family, heterozygous for these systems over 6 generations. Recombination next to the S locus occurred mainly in pigs belonging to this particular family. From this investigation the position of the S locus is proved to be outwith the Phi-Pgd region, next to Phi . Therefore the gene sequence S - Phi - Hal -H- Po2 -Pgd is proposed. Higher recombination rates were observed in the female parental line of the multiheterozygous family when compared to the male parental line. Additional data from animals, unrelated to this strain, confirm the evidence of close linkage of the S system to the nearest marker loci. 相似文献
5.
《Cell reports》2020,30(1):98-111.e5
- Download : Download high-res image (124KB)
- Download : Download full-size image
6.
7.
Brd G. Stokke Torgeir Nygrd Ulla Falkdalen Hans C. Pedersen Roel May 《Ecology and evolution》2020,10(12):5670-5679
- Birds colliding with turbine rotor blades is a well‐known negative consequence of wind‐power plants. However, there has been far less attention to the risk of birds colliding with the turbine towers, and how to mitigate this risk.
- Based on data from the Smøla wind‐power plant in Central Norway, it seems highly likely that willow ptarmigan (the only gallinaceous species found on the island) is prone to collide with turbine towers. By employing a BACI‐approach, we tested if painting the lower parts of turbine towers black would reduce the collision risk.
- Overall, there was a 48% reduction in the number of recorded ptarmigan carcasses per search at painted turbines relative to neighboring control (unpainted) ones, with significant variation both within and between years.
- Using contrast painting to the turbine towers resulted in significantly reduced number of ptarmigan carcasses found, emphasizing the effectiveness of such a relatively simple mitigation measure.
8.
Maturity Onset Diabetes of the Young (MODY) is a heterogeneous group of genetic diseases characterized by a primary defect in insulin secretion and hyperglycemia, non-ketotic disease, monogenic autosomal dominant mode of inheritance, age at onset less than 25 years, and lack of auto-antibodies. It accounts for 2–5% of all cases of non-type 1 diabetes. MODY subtype 2 is caused by mutations in the glucokinase (GCK) gene. In this study, we sequenced the GCK gene of two volunteers with clinical diagnosis for MODY2 and we were able to identify four mutations including one for a premature stop codon (c.76C>T). Based on these results, we have developed a specific PCR-RFLP assay to detect this mutation and tested 122 related volunteers from the same family. This mutation in the GCK gene was detected in 21 additional subjects who also had the clinical features of this genetic disease. In conclusion, we identified new GCK gene mutations in a Brazilian family of Italian descendance, with one due to a premature stop codon located in the second exon of the gene. We also developed a specific assay that is fast, cheap and reliable to detect this mutation. Finally, we built a molecular ancestry model based on our results for the migration of individuals carrying this genetic mutation from Northern Italy to Brazil. 相似文献
9.
《Journal of molecular biology》2021,433(19):167162
Many proteins that can assemble into higher order structures termed amyloids can also concentrate into cytoplasmic inclusions via liquid–liquid phase separation. Here, we study the assembly of human Golgi-Associated plant Pathogenesis Related protein 1 (GAPR-1), an amyloidogenic protein of the Cysteine-rich secretory proteins, Antigen 5, and Pathogenesis-related 1 proteins (CAP) protein superfamily, into cytosolic inclusions in Saccharomyces cerevisiae. Overexpression of GAPR-1-GFP results in the formation GAPR-1 oligomers and fluorescent inclusions in yeast cytosol. These cytosolic inclusions are dynamic and reversible organelles that gradually increase during time of overexpression and decrease after promoter shut-off. Inclusion formation is, however, a regulated process that is influenced by factors other than protein expression levels. We identified N-myristoylation of GAPR-1 as an important determinant at early stages of inclusion formation. In addition, mutations in the conserved metal-binding site (His54 and His103) enhanced inclusion formation, suggesting that these residues prevent uncontrolled protein sequestration. In agreement with this, we find that addition of Zn2+ metal ions enhances inclusion formation. Furthermore, Zn2+ reduces GAPR-1 protein degradation, which indicates stabilization of GAPR-1 in inclusions. We propose that the properties underlying both the amyloidogenic properties and the reversible sequestration of GAPR-1 into inclusions play a role in the biological function of GAPR-1 and other CAP family members. 相似文献
10.
R Liang 《Biochemical and biophysical research communications》1984,120(3):741-746
Primary cell cultures were prepared from breast muscles of 11 day 4 hour-embryonic chicks. Cytoplasmic RNAs were isolated from the cultured cells at various time intervals from day 3 to day 8. A [P32] DNA probe complementary to messenger RNA of myosin heavy chain was used to hybridize with the RNAs after gel electrophoresis. A transient species of polyadenylated RNA with a decreased mobility in electrophoresis was detected during a period of time when contractions of syncytial fibers were first observed. 相似文献