全文获取类型
收费全文 | 154323篇 |
免费 | 148076篇 |
国内免费 | 33497篇 |
出版年
2021年 | 4599篇 |
2020年 | 3602篇 |
2019年 | 6035篇 |
2018年 | 5617篇 |
2017年 | 4477篇 |
2016年 | 5614篇 |
2015年 | 7704篇 |
2014年 | 8643篇 |
2013年 | 9270篇 |
2012年 | 10738篇 |
2011年 | 10460篇 |
2010年 | 8849篇 |
2009年 | 13202篇 |
2008年 | 8377篇 |
2007年 | 7868篇 |
2006年 | 6296篇 |
2005年 | 5760篇 |
2004年 | 5263篇 |
2003年 | 4495篇 |
2002年 | 4944篇 |
2001年 | 5953篇 |
2000年 | 3706篇 |
1999年 | 8201篇 |
1998年 | 9639篇 |
1997年 | 9765篇 |
1996年 | 9076篇 |
1995年 | 9289篇 |
1994年 | 8617篇 |
1993年 | 8179篇 |
1992年 | 8459篇 |
1991年 | 8342篇 |
1990年 | 9097篇 |
1989年 | 8302篇 |
1988年 | 7499篇 |
1987年 | 6549篇 |
1986年 | 6043篇 |
1985年 | 5439篇 |
1984年 | 4196篇 |
1983年 | 3390篇 |
1982年 | 3635篇 |
1981年 | 3296篇 |
1980年 | 3211篇 |
1979年 | 3372篇 |
1978年 | 3037篇 |
1977年 | 2978篇 |
1976年 | 2787篇 |
1974年 | 2552篇 |
1973年 | 2531篇 |
1972年 | 2865篇 |
1971年 | 2629篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
101.
Recent studies have revealed an unexpected synergism between two seemingly unrelated protein families: CCN matricellular proteins
and the tumor necrosis factor (TNF) family of cytokines. CCN proteins are dynamically expressed at sites of injury repair
and inflammation, where TNF cytokines are also expressed. Although TNFα is an apoptotic inducer in some cancer cells, it activates
NFκB to promote survival and proliferation in normal cells, and its cytotoxicity requires inhibition of de novo protein synthesis
or NFκB signaling. The presence of CCN1, CCN2, or CCN3 overrides this requirement and unmasks the apoptotic potential of TNFα,
thus converting TNFα from a proliferation-promoting protein into an apoptotic inducer. These CCN proteins also enhance the
cytotoxicity of other TNF cytokines, including LTα, FasL, and TRAIL. Mechanistically, CCNs function through integrin α6β1 and the heparan sulfate proteoglycan (HSPG) syndecan-4 to induce reactive oxygen species (ROS) accumulation, which is essential
for apoptotic synergism. Mutant CCN1 proteins defective for binding α6β1-HSPGs are unable to induce ROS or apoptotic synergism with TNF cytokines. Further, knockin mice that express an α6β1-HSPG-binding defective CCN1 are blunted in TNFα- and Fas-mediated apoptosis, indicating that CCN1 is a physiologic regulator
of these processes. These findings implicate CCN proteins as contextual regulators of the inflammatory response by dictating
or enhancing the cytotoxicity of TNFα and related cytokines. 相似文献
102.
103.
104.
M. P. De Leon T. Yanagi M. Kikuchi J. Mu O. Ayau V. Matta M. Paz S. Juarez H. Kanbara I. Tada K. Hirayama 《International journal for parasitology》1998,28(12):1867-1874
Fifty fresh isolates of Trypanosoma cruzi from Triatoma dimidiata vectors and 31 from patients with Chagas disease were analysed for DNA polymorphisms within the 432-bp core region of the cruzipain gene which encodes the active site of cathepsin L-like cystein proteinase. The cruzipain gene showed signs of polymorphism consisting of four different DNA sequences in Central and South American isolates of T. cruzi. The PCR fragments of Guatemalan isolates could be divided into three groups, Groups 1, 2 and 3, based on different patterns of single-stranded DNA conformation polymorphism. All of the strains isolated from Brazil, Chile, and Paraguay, except for the CL strain, showed a Group 4 pattern. Two to four isolates from each group were analysed by cloning and sequencing. A silent mutation occurred between Groups 1 and 2, and five nucleotides and two aa substitutions were detected between Groups 1 and 3. The DNA sequence of Group 4 contained five nucleotides and one aa substitution from Group 1. All of the DNA sequences corresponded well with the single-stranded DNA conformation polymorphism. The Group 1 isolates, the majority in the Guatemalan population (70/81, 86.4%), were isolated from both triatomines and humans, but Group 3 were isolated only from humans. Moreover, the Group 2 isolates were detected only in triatomine vectors (9/50; 18%), but never in humans (0/32, P<0.05) suggesting that this group has an independent life-cycle in sylvatic animals and is maintained by reservoir hosts other than humans. 相似文献
105.
N. J. Belshaw S. Hakola H. Nevalainen M. Penttil? P. Suominen D. B. Archer 《Molecular & general genetics : MGG》1997,256(1):18-27
Three DNA fragments, trs1, 2 and 3, were isolated from the Trichoderma reesei genome on the basis of their ability to promote autonomous replication of plasmids in Saccharomyces cerevisiae. Each trs element bound specifically to the isolated T. reesei nuclear matrix in vitro, and two of them bound in vivo, indicating that they are matrix attachment regions (MARs). A similar
sequence previously isolated from Aspergillus nidulans (ans1) was also shown to bind specifically to the T. reesei nuclear matrix in vitro. The T. reesei MARs are AT-rich sequences containing 70%, 86% and 73% A+T over 2.9, 0.8 and 3.7 kb, respectively for trs1, 2 and 3. They exhibited no significant sequence homology, but were shown to contain a number of sequence motifs that occur frequently
in many MARs identified in other eukaryotes. However, these motifs occurred as frequently in the trs elements as in randomly generated sequences with the same A+T content. trs1 and 3 were shown to be present as single copies in the T. reesei genome. The presence of the trs elements in transforming plasmids enhanced the frequency of integrative transformation of T. reesei up to five fold over plasmids without a trs. No evidence was obtained to suggest that the trs elements promoted efficient replication of plasmids in T. reseei. A mechanism for the enhancement of transformation frequency by the trs elements is proposed.
Received: 1 March 1997 / Accepted: 13 May 1997 相似文献
106.
107.
108.
Comparisons among 16S rRNA sequences from various eubacteria reveal a natural relationship between the bacteroides (represented by the Bacteroides fragilis sequence) and a phylogenetic unit that comprises the flavobacteria, cytophagae, flexibacteria, and others (represented by the Flavobacterium heparinum sequence). Although the relationship is not a close one, it is, nevertheless, specific. rRNAs from these two organisms are not only closer to one another in overall sequence than they are to outgroup species (such as Bacillus subtilis, Escherichia coli, Desulfovibrio desulfuricans, and Agrobacterium tumefaciens), but they show common idiosyncrasies (i.e., derived characteristics) in both rRNA sequences and higher-order structures. 相似文献
109.