全文获取类型
收费全文 | 2701篇 |
免费 | 165篇 |
专业分类
2866篇 |
出版年
2022年 | 18篇 |
2021年 | 28篇 |
2020年 | 18篇 |
2019年 | 27篇 |
2018年 | 35篇 |
2017年 | 32篇 |
2016年 | 56篇 |
2015年 | 74篇 |
2014年 | 104篇 |
2013年 | 180篇 |
2012年 | 168篇 |
2011年 | 150篇 |
2010年 | 86篇 |
2009年 | 70篇 |
2008年 | 152篇 |
2007年 | 113篇 |
2006年 | 134篇 |
2005年 | 124篇 |
2004年 | 131篇 |
2003年 | 104篇 |
2002年 | 89篇 |
2001年 | 93篇 |
2000年 | 95篇 |
1999年 | 84篇 |
1998年 | 29篇 |
1997年 | 18篇 |
1996年 | 12篇 |
1995年 | 20篇 |
1994年 | 16篇 |
1993年 | 16篇 |
1992年 | 47篇 |
1991年 | 45篇 |
1990年 | 42篇 |
1989年 | 53篇 |
1988年 | 48篇 |
1987年 | 42篇 |
1986年 | 43篇 |
1985年 | 39篇 |
1984年 | 28篇 |
1983年 | 10篇 |
1982年 | 28篇 |
1981年 | 13篇 |
1979年 | 17篇 |
1978年 | 18篇 |
1977年 | 12篇 |
1974年 | 13篇 |
1973年 | 12篇 |
1972年 | 8篇 |
1969年 | 16篇 |
1967年 | 7篇 |
排序方式: 共有2866条查询结果,搜索用时 0 毫秒
991.
The major damage to DNA caused by alkylating agents involves the formation of O(6)-methylguanine (O(6)-meG). Almost all species possess O(6)-methylguanine-DNA-methyltransferase (Ogt) to repair such damage. Ogt repairs O(6)-meG lesions in DNA by stoichiometric transfer of the methyl group to a cysteine residue in its active site (PCHR). Thermus thermophilus HB8 has an Ogt homologue, TTHA1564, but in this case an alanine residue replaces cysteine in the putative active site. To reveal the possible function of TTHA1564 in processing O(6)-meG-containing DNA, we characterized the biochemical properties of TTHA1564. No methyltransferase activity for synthetic O(6)-meG-containing DNA could be detected, indicating TTHA1564 is an alkyltransferase-like protein. Nevertheless, gel shift assays showed that TTHA1564 can bind to DNA containing O(6)-meG with higher affinity (9-fold) than normal (unmethylated) DNA. Experiments using a fluorescent oligonucleotide suggested that TTHA1564 recognizes O(6)-meG in DNA using the same mechanism as other Ogts. We then investigated whether TTHA1564 functions as a damage sensor. Pull-down assays identified 20 proteins, including a nucleotide excision repair protein UvrA, which interacts with TTHA1564. Interaction of TTHA1564 with UvrA was confirmed using a surface plasmon resonance assay. These results suggest the possible involvement of TTHA1564 in DNA repair pathways. 相似文献
992.
The DNA-binding protein HU is ubiquitous in the prokaryotic cell. It is a major protein component of isolated nucleoids and is believed to control the tertiary structure of prokaryotic DNA. The Bacillus stearothermophilus HU (BstHU) mutants obtained by mutagenesis have been investigated. Crystallization experiments of BstHU-K38N (Lys38 is substituted with Asn) resulted in two forms of crystals suitable for high-resolution x-ray analysis. The first form belongs to the monoclinic space group C2 with unit-cell dimensions of a = 90.1 A, b = 43.5 A, c = 63.7 A, and beta = 135.1 degrees, and it diffracts x rays to 1.5-A resolution. The second form belongs to the tetragonal space group I41 with a = b = 62.6 A and c = 43.3 A, and it diffracts up to 1.8-A resolution. 相似文献
993.
Tsumoto H Takahashi K Suzuki T Nakagawa H Kohda K Miyata N 《Bioorganic & medicinal chemistry letters》2008,18(2):657-660
We report the syntheses of C(60)-based active esters and the coupling of their C(60) moiety to various amines or alcohols. Methano[60]fullerene carboxylic acid was activated by esterification with N-hydroxysuccinimide (NHS) or pentafluorophenol (PFP) and the active esters were isolated. Reactions of the active esters with amines or alcohols proceeded easily to give a variety of compounds having the C(60) moiety. 相似文献
994.
The Tetrahymena Ca2+-binding protein of 25 kDa (TCBP-25) is a calmodulin family protein containing four EF-hand type calcium-binding domains. TCBP-25 is localized in the whole cell cortex and around both the migratory and stationary pronuclei at the pronuclear exchange stage during conjugation. TCBP-25 is expected to play an important role in conjugation, though its function during sexual reproduction has not been elucidated. According to the localization of this protein and its timing, three possible roles of TCBP-25 are proposed. TCBP-25 may play a role in 1) differentiating the two functional pronuclei from the degenerative post-meiotic nuclei, 2) the process of pronuclear exchange and 3) pronuclear fusion. To test these hypotheses, the localization of TCBP-25 in conjugation mutants (cnj10, cnj7 and bcd2) was examined. The results ruled out the first and the third hypotheses and suggested that TCBP-25 may play a role in pronuclear exchange. In the next step we succeeded in reducing expression of the TCBP-25 gene using the antisense ribosome system, and we analyzed the phenotype of the transformants. The knock down of TCBP-25 function also suggests that TCBP-25 plays a role in the pronuclear exchange and in the maintenance of cell shape. 相似文献
995.
996.
Shibata H Yoshioka Y Ohkawa A Abe Y Nomura T Mukai Y Nakagawa S Taniai M Ohta T Mayumi T Kamada H Tsunoda S Tsutsumi Y 《Cytokine》2008,44(2):229-233
Tumor necrosis factor-alpha (TNF-alpha) is critically involved in a wide variety of inflammatory pathologies, such as hepatitis, via the TNF receptor-1 (TNFR1). To develop TNFR1-targeted anti-inflammatory drugs, we have already succeeded in creating a TNFR1-selective antagonistic mutant TNF-alpha (R1antTNF) and shown that R1antTNF efficiently inhibits TNF-alpha/TNFR1-mediated biological activity in vitro. In this study, we examined the therapeutic effect of R1antTNF in acute hepatitis using two independent experimental models, induced by carbon tetrachloride (CCl(4)) or concanavalin A (ConA). In a CCl(4)-induced model, treatment with R1antTNF significantly inhibited elevation in the serum level of ALT (alanine aminotransferase), a marker for liver damage. In a ConA-induced T-cell-mediated hepatitis model, R1antTNF also inhibited the production of serum immune activated markers such as IL-2 and IL-6. These R1antTNF-mediated therapeutic effects were as good as or better than those obtained using conventional anti-TNF-alpha antibody therapy. Our results suggest that R1antTNF may be a clinically useful TNF-alpha antagonist in hepatitis. 相似文献
997.
998.
Understanding regulatory mechanisms of protein synthesis in eukaryotes is essential for the accurate annotation of genome sequences. Kozak reported that the nucleotide sequence GCCGCC(A/G)CCAUGG (AUG is the initiation codon) was frequently observed in vertebrate genes and that this 'consensus' sequence enhanced translation initiation. However, later studies using invertebrate, fungal and plant genes reported different 'consensus' sequences. In this study, we conducted extensive comparative analyses of nucleotide sequences around the initiation codon by using genomic data from 47 eukaryote species including animals, fungi, plants and protists. The analyses revealed that preferred nucleotide sequences are quite diverse among different species, but differences between patterns of nucleotide bias roughly reflect the evolutionary relationships of the species. We also found strong biases of A/G at position -3, A/C at position -2 and C at position +5 that were commonly observed in all species examined. Genes with higher expression levels showed stronger signals, suggesting that these nucleotides are responsible for the regulation of translation initiation. The diversity of preferred nucleotide sequences around the initiation codon might be explained by differences in relative contributions from two distinct patterns, GCCGCCAUG and AAAAAAAUG, which implies the presence of multiple molecular mechanisms for controlling translation initiation. 相似文献
999.
Kuroki H Nakagawa Y Mori K Kobayashi M Yasura K Okamoto Y Suzuki T Nishitani K Nakamura T 《Arthritis research & therapy》2008,10(4):R78
Introduction
There is a lack of data relating the macroscopic appearance of cartilage to its ultrasound properties. The purpose of the present study was to evaluate degenerated cartilage and healthy-looking cartilage using an ultrasound system. 相似文献1000.