全文获取类型
收费全文 | 3513篇 |
免费 | 46篇 |
国内免费 | 145篇 |
出版年
2023年 | 10篇 |
2022年 | 17篇 |
2021年 | 33篇 |
2020年 | 25篇 |
2019年 | 36篇 |
2018年 | 31篇 |
2017年 | 24篇 |
2016年 | 35篇 |
2015年 | 73篇 |
2014年 | 274篇 |
2013年 | 344篇 |
2012年 | 294篇 |
2011年 | 311篇 |
2010年 | 227篇 |
2009年 | 141篇 |
2008年 | 141篇 |
2007年 | 138篇 |
2006年 | 119篇 |
2005年 | 143篇 |
2004年 | 96篇 |
2003年 | 103篇 |
2002年 | 82篇 |
2001年 | 65篇 |
2000年 | 52篇 |
1999年 | 94篇 |
1998年 | 71篇 |
1997年 | 74篇 |
1996年 | 67篇 |
1995年 | 105篇 |
1994年 | 106篇 |
1993年 | 71篇 |
1992年 | 68篇 |
1991年 | 49篇 |
1990年 | 30篇 |
1989年 | 11篇 |
1988年 | 15篇 |
1987年 | 12篇 |
1986年 | 11篇 |
1985年 | 11篇 |
1984年 | 8篇 |
1983年 | 22篇 |
1982年 | 12篇 |
1981年 | 12篇 |
1980年 | 12篇 |
1979年 | 11篇 |
1978年 | 3篇 |
1977年 | 6篇 |
1976年 | 3篇 |
1973年 | 1篇 |
1972年 | 4篇 |
排序方式: 共有3704条查询结果,搜索用时 15 毫秒
1.
This paper is concerned with gene survival in a population which may increase without density dependence according to a generalization of the Moran model for haploid individuals. A selective advantage to one allele and the possibility of differential reproductive rates are allowed. Simple conditions are given for ultimate homozygosity to be certain and for the possibility of ultimate polymorphism. The results complement and extend those of Heyde (1981, 1982). 相似文献
2.
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
3.
《DNA Repair》2017
Human PrimPol is a recently discovered bifunctional enzyme that displays DNA template-directed primase and polymerase activities. PrimPol has been implicated in nuclear and mitochondrial DNA replication fork progression and restart as well as DNA lesion bypass. Published evidence suggests that PrimPol is a Mn2+-dependent enzyme as it shows significantly improved primase and polymerase activities when binding Mn2+, rather than Mg2+, as a divalent metal ion cofactor. Consistently, our fluorescence anisotropy assays determined that PrimPol binds to a primer/template DNA substrate with affinities of 29 and 979 nM in the presence of Mn2+ and Mg2+, respectively. Our pre-steady-state kinetic analysis revealed that PrimPol incorporates correct dNTPs with 100-fold higher efficiency with Mn2+ than with Mg2+. Notably, the substitution fidelity of PrimPol in the presence of Mn2+ was determined to be in the range of 3.4 × 10−2 to 3.8 × 10−1, indicating that PrimPol is an error-prone polymerase. Furthermore, we kinetically determined the sugar selectivity of PrimPol to be 57–1800 with Mn2+ and 150–4500 with Mg2+, and found that PrimPol was able to incorporate the triphosphates of two anticancer drugs (cytarabine and gemcitabine), but not two antiviral drugs (emtricitabine and lamivudine). 相似文献
4.
5.
Leslie A. Holladay 《Biophysical chemistry》1985,22(4):281-284
The unfolding at pH 8 of chicken cardiac aquometmyoglobin was examined as a function of temperature and concentration of guanidinium chloride using the two-state model. The isothermal unfolding data at 25°C were fitted to Tanford's transfer model and the binding model of Aune and Tanford. The estimates obtained for ΔGD) were virtually identical, viz., 8.3 ±0.3 kcal mol?1. The chicken metmyoglobin is thus some 5.3 kcal mol?1 less stable than that of sperm whale metmyoglobin. The unfolding parameters α and Δn were decreased 20% from those of mammalian myoglobins thus far examined, suggesting nonidentity of native conformations. The apparent enthalpy change on unfolding was dependent on both temperature and denaturant concentration. The decreases in the isothermal unfolding parameters from those of sperm whale are principally assigned to three of the 46 sequence changes. 相似文献
6.
7.
Peter W. Wilson Katie E. Osterday Aaron F. Heneghan Anthony D. J. Haymet 《The Journal of biological chemistry》2010,285(45):34741-34745
In this study, we examined the effects that antifreeze proteins have on the supercooling and ice-nucleating abilities of aqueous solutions. Very little information on such nucleation currently exists. Using an automated lag time apparatus and a new analysis, we show several dilution series of Type I antifreeze proteins. Our results indicate that, above a concentration of ∼8 mg/ml, ice nucleation is enhanced rather than hindered. We discuss this unexpected result and present a new hypothesis outlining three components of polar fish blood that we believe affect its solution properties in certain situations. 相似文献
8.
Strategies for signal amplification in nucleic acid detection 总被引:3,自引:0,他引:3
S. Calin Andras J. Brian Power Edward C. Cocking Michael R. Davey 《Molecular biotechnology》2001,19(1):29-44
Many aspects of molecular genetics necessitate the detection of nucleic acid sequences. Current approaches involving target
amplification (in situ PCR, Primed in situ Labeling, Self-Sustained Sequence Replication, Strand Displacement Amplification), probe amplification (Ligase Chain Reaction,
Padlock Probes, Rolling Circle Amplification) and signal amplification (Tyramide Signal Amplification, Branched DNA Amplification)
are summarized in the present review, together with their advantages and limitations. 相似文献
9.
10.
Markus Pech Thomas Spreter Roland Beckmann Birgitta Beatrix 《The Journal of biological chemistry》2010,285(25):19679-19687
Nascent polypeptide-associated complex (NAC) was identified in eukaryotes as the first cytosolic factor that contacts the nascent polypeptide chain emerging from the ribosome. NAC is present as a homodimer in archaea and as a highly conserved heterodimer in eukaryotes. Mutations in NAC cause severe embryonically lethal phenotypes in mice, Drosophila melanogaster, and Caenorhabditis elegans. In the yeast Saccharomyces cerevisiae NAC is quantitatively associated with ribosomes. Here we show that NAC contacts several ribosomal proteins. The N terminus of βNAC, however, specifically contacts near the tunnel exit ribosomal protein Rpl31, which is unique to eukaryotes and archaea. Moreover, the first 23 amino acids of βNAC are sufficient to direct an otherwise non-associated protein to the ribosome. In contrast, αNAC (Egd2p) contacts Rpl17, the direct neighbor of Rpl31 at the ribosomal tunnel exit site. Rpl31 was also recently identified as a contact site for the SRP receptor and the ribosome-associated complex. Furthermore, in Escherichia coli peptide deformylase (PDF) interacts with the corresponding surface area on the eubacterial ribosome. In addition to the previously identified universal adapter site represented by Rpl25/Rpl35, we therefore refer to Rpl31/Rpl17 as a novel universal docking site for ribosome-associated factors on the eukaryotic ribosome. 相似文献