全文获取类型
收费全文 | 1307篇 |
免费 | 206篇 |
出版年
2022年 | 12篇 |
2021年 | 33篇 |
2019年 | 15篇 |
2018年 | 18篇 |
2017年 | 17篇 |
2016年 | 37篇 |
2015年 | 46篇 |
2014年 | 39篇 |
2013年 | 38篇 |
2012年 | 67篇 |
2011年 | 66篇 |
2010年 | 53篇 |
2009年 | 52篇 |
2008年 | 51篇 |
2007年 | 43篇 |
2006年 | 46篇 |
2005年 | 47篇 |
2004年 | 47篇 |
2003年 | 38篇 |
2002年 | 44篇 |
2001年 | 42篇 |
2000年 | 46篇 |
1999年 | 27篇 |
1998年 | 24篇 |
1997年 | 16篇 |
1996年 | 12篇 |
1994年 | 13篇 |
1993年 | 19篇 |
1992年 | 23篇 |
1991年 | 14篇 |
1990年 | 27篇 |
1989年 | 35篇 |
1988年 | 22篇 |
1987年 | 17篇 |
1986年 | 23篇 |
1985年 | 23篇 |
1984年 | 24篇 |
1983年 | 14篇 |
1981年 | 16篇 |
1979年 | 14篇 |
1978年 | 16篇 |
1977年 | 18篇 |
1976年 | 16篇 |
1975年 | 17篇 |
1974年 | 18篇 |
1973年 | 23篇 |
1972年 | 17篇 |
1971年 | 18篇 |
1970年 | 14篇 |
1967年 | 15篇 |
排序方式: 共有1513条查询结果,搜索用时 15 毫秒
1.
2.
3.
Kathryn S. Evans Janneke Wit Lewis Stevens Steffen R. Hahnel Briana Rodriguez Grace Park Mostafa Zamanian Shannon C. Brady Ellen Chao Katherine Introcaso Robyn E. Tanny Erik C. Andersen 《PLoS pathogens》2021,17(3)
Parasitic nematodes cause a massive worldwide burden on human health along with a loss of livestock and agriculture productivity. Anthelmintics have been widely successful in treating parasitic nematodes. However, resistance is increasing, and little is known about the molecular and genetic causes of resistance for most of these drugs. The free-living roundworm Caenorhabditis elegans provides a tractable model to identify genes that underlie resistance. Unlike parasitic nematodes, C. elegans is easy to maintain in the laboratory, has a complete and well annotated genome, and has many genetic tools. Using a combination of wild isolates and a panel of recombinant inbred lines constructed from crosses of two genetically and phenotypically divergent strains, we identified three genomic regions on chromosome V that underlie natural differences in response to the macrocyclic lactone (ML) abamectin. One locus was identified previously and encodes an alpha subunit of a glutamate-gated chloride channel (glc-1). Here, we validate and narrow two novel loci using near-isogenic lines. Additionally, we generate a list of prioritized candidate genes identified in C. elegans and in the parasite Haemonchus contortus by comparison of ML resistance loci. These genes could represent previously unidentified resistance genes shared across nematode species and should be evaluated in the future. Our work highlights the advantages of using C. elegans as a model to better understand ML resistance in parasitic nematodes. 相似文献
4.
5.
The effect of the suspensor and gibberellic acid on Phaseolus vulgaris embryo protein synthesis 总被引:2,自引:0,他引:2
The role of the suspensor in the early development of the dicot embryo has been described as merely an anchor or, conversely, as the major route of nutrients into the embryo. In order to further elucidate the role of the suspensor we have examined protein synthesis in early 0.2-mm and late heart stage 0.5-mm Phaseolus vulgaris (var. Taylor's Horticultural) embryos in tissue culture. Protein synthesis was examined in embryos and suspensors. Our results showed that in 0.2-mm embryos virtually all protein synthesis was dependent on an attached suspensor. Maximum protein synthesis in 0.5-mm embryos was observed when embryos were cultured attached to the suspensor. The levels were moderately decreased when the embryo was cultured detached from or without the suspensor. Gibberellic acid at 10(-6) to 10(-7) M elicited the same protein diversity and greater [35S]methionine incorporation than did the attached suspensor in 0.2-mm embryos. Embryos of 0.5 mm did not appear to be differentially responsive to various gibberellin concentrations. 相似文献
6.
7.
Nerve growth factor treatment or cAMP elevation reduces Ca2+/calmodulin-dependent protein kinase III activity in PC12 cells 总被引:3,自引:0,他引:3
A C Nairn R A Nichols M J Brady H C Palfrey 《The Journal of biological chemistry》1987,262(29):14265-14272
Ca2+/calmodulin-dependent protein kinase III (Ca2+/CaM kinase III) phosphorylates a protein of Mr = 100,000 (the 100-kDa protein), a major substrate for Ca2+/CaM-dependent protein phosphorylation found in many mammalian tissues and cell lines (Nairn, A.C., Baghat, B., and Palfrey, H.C. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 7939-7943). Treatment of PC12 cells with nerve growth factor (NGF) or forskolin resulted in a decrease in the depolarization-dependent phosphorylation of the 100-kDa protein in intact cells and in a decrease in the Ca2+/CaM-dependent phosphorylation of the 100-kDa protein in cytosolic extracts. In experiments using cytosolic extracts, the initial effect of NGF on the phosphorylation of the 100-kDa protein was observed in less than 1 h, was maximal (70% decrease) after 12 h, and began to recover after 24 h. The effect of forskolin was more rapid and the maximal effect was greater (90-95% decrease). Decreased Ca2+/CaM kinase III activity was also found in PC12 cells treated with epidermal growth factor, 2-chloroadenosine plus isobutylmethylxanthine, or dibutyryl cAMP. The effect of forskolin did not reverse unless it was removed. Cycloheximide blocked the recovery of Ca2+/CaM kinase III activity observed following the removal of forskolin but did not affect the ability of forskolin to reduce kinase activity. Short-term treatment with phorbol ester had little effect on Ca2+/CaM kinase III activity; long-term treatment with phorbol ester, which results in the disappearance of enzymatically detectable protein kinase C, had no effect on the ability of NGF or 2-chloroadenosine to reduce Ca2+/CaM kinase III activity. The level of the 100-kDa protein as determined by immunological techniques was not changed by any treatment. These results suggested that the effect of treatment of PC12 cells with NGF or forskolin was to reduce the level of Ca2+/CaM kinase III per se. 相似文献
8.
Evolution of the 28S ribosomal RNA gene in anurans: regions of variability and their phylogenetic implications 总被引:1,自引:0,他引:1
Fifteen restriction sites were mapped to the 28S ribosomal RNA gene of
individuals representing 54 species of frogs, two species of salamanders, a
caecilian, and a lungfish. Eight of these sites were present in all species
examined, and two were found in all but one species. Alignment of these
conserved restriction sites revealed, among anuran 28S rRNA genes, five
regions of major length variation that correspond to four of 12 previously
identified divergent domains of this gene. One of the divergent domains
(DD8) consists of two regions of length variation separated by a short
segment that is conserved at least throughout tetrapods. Most of the
insertions, deletions, and restriction-site variations identified in the
28S gene will require sequence-level analysis for a detailed reconstruction
of their history. However, an insertion in DD9 that is coextensive with
frogs in the suborder Neobatrachia, a BstEII site that is limited to
representatives of two leptodactylid subfamilies, and a deletion in DD10
that is found only in three ranoid genera are probably synapomorphies.
相似文献
9.
Identification of a novel sequence that governs both polyadenylation and alternative splicing in region E3 of adenovirus. 总被引:13,自引:0,他引:13 下载免费PDF全文
Region E3 encodes four major overlapping mRNAs with different splicing patterns. There are two poly(A) sites, an upstream site called E3A and a downstream site called E3B. We have analyzed virus mutants with deletions or insertions in E3 in order to identify sequences that function in the alternative processing of E3 pre-mRNAs, and to understand what determines which poly(A) sites and which splice sites are used. In previous studies we established that the 5' boundary of the E3A poly(A) signal is at an ATTAAA sequence. We now show, using viable virus mutants, that the 3' boundary of the E3A signal is located within 47-62 nucleotides (nt) downstream of the ATTAAA (17-32 nt downstream of the last microheterogenous poly(A) addition site). Our data further suggest that the spacing between the ATTAAA, the cleavage sites, and the essential downstream sequences may be important in E3A 3' end formation. Of particular interest, these mutants suggest a novel mechanism for the control of alternative pre-mRNA processing. Mutants which are almost completely defective in E3A 3' end formation display greatly increased use of a 3' splice site located 4 nt upstream of the ATTAAA. The mRNA that uses this 3' splice site is polyadenylated at the E3B poly(A) site. We suggest, for this particular case, that alternative pre-mRNA processing could be determined by a competition between trans-acting factors that function in E3A 3' end formation or in splicing. These factors could compete for overlapping sequences in pre-mRNA. 相似文献
10.