全文获取类型
收费全文 | 6635篇 |
免费 | 308篇 |
国内免费 | 8篇 |
专业分类
6951篇 |
出版年
2023年 | 13篇 |
2022年 | 31篇 |
2021年 | 66篇 |
2020年 | 41篇 |
2019年 | 60篇 |
2018年 | 93篇 |
2017年 | 80篇 |
2016年 | 106篇 |
2015年 | 185篇 |
2014年 | 240篇 |
2013年 | 499篇 |
2012年 | 398篇 |
2011年 | 404篇 |
2010年 | 257篇 |
2009年 | 272篇 |
2008年 | 449篇 |
2007年 | 430篇 |
2006年 | 414篇 |
2005年 | 472篇 |
2004年 | 463篇 |
2003年 | 433篇 |
2002年 | 393篇 |
2001年 | 48篇 |
2000年 | 52篇 |
1999年 | 54篇 |
1998年 | 94篇 |
1997年 | 71篇 |
1996年 | 79篇 |
1995年 | 79篇 |
1994年 | 50篇 |
1993年 | 61篇 |
1992年 | 50篇 |
1991年 | 44篇 |
1990年 | 30篇 |
1989年 | 36篇 |
1988年 | 24篇 |
1987年 | 36篇 |
1986年 | 28篇 |
1985年 | 23篇 |
1984年 | 34篇 |
1983年 | 29篇 |
1982年 | 39篇 |
1981年 | 30篇 |
1980年 | 22篇 |
1979年 | 28篇 |
1978年 | 26篇 |
1977年 | 16篇 |
1976年 | 21篇 |
1975年 | 9篇 |
1973年 | 9篇 |
排序方式: 共有6951条查询结果,搜索用时 15 毫秒
81.
Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21 总被引:3,自引:0,他引:3
Kurosu H Choi M Ogawa Y Dickson AS Goetz R Eliseenkova AV Mohammadi M Rosenblatt KP Kliewer SA Kuro-o M 《The Journal of biological chemistry》2007,282(37):26687-26695
82.
Yamagata K Senokuchi T Lu M Takemoto M Fazlul Karim M Go C Sato Y Hatta M Yoshizawa T Araki E Miyazaki J Song WJ 《Biochemical and biophysical research communications》2011,(3):620-625
Bone homeostasis is maintained by a dynamic balance between bone resorption by osteoclasts and bone formation by osteoblasts. Since excessive osteoclast activity is implicated in pathological bone resorption, understanding the mechanism underlying osteoclast differentiation, function and survival is of both scientific and clinical importance. Osteoclasts are monocyte/macrophage lineage cells with a short life span that undergo rapid apoptosis, the rate of which critically determines the level of bone resorption in vivo. However, the molecular basis of rapid osteoclast apoptosis remains obscure. Here we report the role of a BH3-only protein, Noxa (encoded by the Pmaip1 gene), in bone homeostasis using Noxa-deficient mice. Among the Bcl-2 family members, Noxa was selectively induced during osteoclastogenesis. Mice lacking Noxa exhibit a severe osteoporotic phenotype due to an increased number of osteoclasts. Noxa deficiency did not have any effect on the number of osteoclast precursor cells or the expression of osteoclast-specific genes, but led to a prolonged survival of osteoclasts. Furthermore, adenovirus-mediated Noxa overexpression remarkably reduced bone loss in a model of inflammation-induced bone destruction. This study reveals Noxa to be a crucial regulator of osteoclast apoptosis, and may provide a molecular basis for a new therapeutic approach to bone diseases. 相似文献
83.
84.
Ishizuka T Yoshida J Yamamoto Y Sumaoka J Tedeschi T Corradini R Sforza S Komiyama M 《Nucleic acids research》2008,36(5):1464-1471
Invasion of two PNA strands to double-stranded DNA is one of the most promising methods to recognize a predetermined site in double-stranded DNA (PNA = peptide nucleic acid). In order to facilitate this 'double-duplex invasion', a new type of PNA was prepared by using chiral PNA monomers in which a nucleobase was bound to the alpha-nitrogen of N-(2-aminoethyl)-d-lysine. These positively charged monomer units, introduced to defined positions in Nielsen's PNAs (poly[N-(2-aminoethyl)glycine] derivatives), promoted the invasion without impairing mismatch-recognizing activity. When pseudo-complementary nucleobases 2,6-diaminopurine and 2-thiouracil were bound to N-(2-aminoethyl)-d-lysine, the invasion successfully occurred even at highly G-C-rich regions [e.g. (G/C)7(A/T)3 and (G/C)8(A/T)2] which were otherwise hardly targeted. Thus, the scope of sequences available as the target site has been greatly expanded. In contrast with the promotion by the chiral PNA monomers derived from N-(2-aminoethyl)-d-lysine, their l-isomers hardly invaded, showing crucial importance of the d-chirality. The promotion of double-duplex invasion by the chiral (d) PNA monomer units was ascribed to both destabilization of PNA/PNA duplex and stabilization of PNA/DNA duplexes. 相似文献
85.
Staphylococcus aureus lipase (SAL) is known to possess broad substrate specificity for triacylglycerides. We found that a sub-minimum inhibitory concentration of farnesol (1000 mg L(-1)) inhibits this lipase activity on a Mueller-Hinton agar containing 1% Tween substrates. A quantitative lipase assay using p-nitrophenyl palmitate (pNPP) revealed that the inhibitory action of farnesol appears to be the result of the inhibition of lipase activity rather than of its secretion into the culture medium. The inhibition was observed in all the tested 8 methicillin-susceptible S. aureus and 31 methicillin-resistant S. aureus clinical isolates. Using homogeneous lipase purified by hydrophobic interaction chromatography, it was revealed that farnesol could competitively inhibit the lipase activity against the substrate pNPP. 相似文献
86.
U6 promoter-driven siRNAs with four uridine 3' overhangs efficiently suppress targeted gene expression in mammalian cells 总被引:98,自引:0,他引:98
The first evidence for gene disruption by double-stranded RNA (dsRNA) came from careful analysis in Caenorhabditis elegans. This phenomenon, called RNA interference (RNAi), was observed subsequently in various organisms, including plants, nematodes, Drosophila, and protozoans. Very recently, it has been reported that in mammalian cells, 21- or 22-nucleotide (nt) RNAs with 2-nt 3' overhangs (small inhibitory RNAs, siRNAs) exhibit an RNAi effect. This is because siRNAs are not recognized by the well-characterized host defense system against viral infections, involving dsRNA-dependent inhibition of protein synthesis. However, the current method for introducing synthetic siRNA into cells by lipofection restricts the range of applications of RNAi as a result of the low transfection efficiencies in some cell types and/or short-term persistence of silencing effects. Here, we report a vector-based siRNA expression system that can induce RNAi in mammalian cells. This technical advance for silencing gene expression not only facilitates a wide range of functional analysis of mammalian genes but might also allow therapeutic applications by means of vector-mediated RNAi. 相似文献
87.
88.
Elevated plasma low-density lipoprotein (LDL) cholesterol is considered as a risk factor for atherosclerosis. Because the hepatic LDL receptor (LDLR) uptakes plasma lipoproteins and lowers plasma LDL cholesterol, the activation of LDLR is a promising drug target for atherosclerosis. In the present study, we identified the naturally occurring alkaloid piperine, as an inducer of LDLR gene expression by screening the effectors of human LDLR promoter. The treatment of HepG2 cells with piperine increased LDLR expression at mRNA and protein levels and stimulated LDL uptake. Subsequent luciferase reporter gene assays revealed that the mutation of sterol regulatory element-binding protein (SREBP)-binding element abolished the piperine-mediated induction of LDLR promoter activity. Further, piperine treatments increased mRNA levels of several SREBP targets and mature forms of SREBPs. However, the piperine-mediated induction of the mature forms of SREBPs was not observed in SRD–15 cells, which lack insulin-induced gene–1 (Insig–1) and Insig–2. Finally, the knockdown of SREBPs completely abolished the piperine-meditated induction of LDLR gene expression in HepG2 cells, indicating that piperine stimulates the proteolytic activation of SREBP and subsequent induction of LDLR expression and activity. 相似文献
89.
90.
Kazuo Imai Norihito Tarumoto Kiyoko Amo Makoto Takahashi Naoya Sakamoto Atsushi Kosaka Yasuyuki Kato Kei Mikita Jun Sakai Takashi Murakami Yutaka Suzuki Shigefumi Maesaki Takuya Maeda 《Parasitology international》2018,67(1):34-37
Cutaneous leishmaniasis (CL) is gaining attention as a public health problem. We present two cases of CL imported from Syria and Venezuela in Japan. We diagnosed them as CL non-invasively by the direct boil loop-mediated isothermal amplification method and an innovative sequencing method using the MinION? sequencer. This report demonstrates that our procedure could be useful for the diagnosis of CL in both clinical and epidemiological settings. 相似文献