全文获取类型
收费全文 | 3989篇 |
免费 | 269篇 |
出版年
2022年 | 8篇 |
2021年 | 29篇 |
2020年 | 22篇 |
2019年 | 39篇 |
2018年 | 55篇 |
2017年 | 62篇 |
2016年 | 84篇 |
2015年 | 116篇 |
2014年 | 162篇 |
2013年 | 199篇 |
2012年 | 267篇 |
2011年 | 253篇 |
2010年 | 177篇 |
2009年 | 171篇 |
2008年 | 263篇 |
2007年 | 233篇 |
2006年 | 241篇 |
2005年 | 243篇 |
2004年 | 254篇 |
2003年 | 199篇 |
2002年 | 236篇 |
2001年 | 61篇 |
2000年 | 85篇 |
1999年 | 74篇 |
1998年 | 50篇 |
1997年 | 42篇 |
1996年 | 42篇 |
1995年 | 37篇 |
1994年 | 37篇 |
1993年 | 30篇 |
1992年 | 54篇 |
1991年 | 36篇 |
1990年 | 34篇 |
1989年 | 46篇 |
1988年 | 37篇 |
1987年 | 32篇 |
1986年 | 31篇 |
1985年 | 26篇 |
1984年 | 24篇 |
1983年 | 21篇 |
1982年 | 13篇 |
1981年 | 11篇 |
1980年 | 8篇 |
1979年 | 24篇 |
1978年 | 15篇 |
1977年 | 12篇 |
1974年 | 9篇 |
1972年 | 7篇 |
1970年 | 7篇 |
1968年 | 5篇 |
排序方式: 共有4258条查询结果,搜索用时 15 毫秒
1.
2.
Genes for the major histocompatibility complex (MHC) were localized by fluorescence in situ hybridization to the long arm of rhesus monkey chromosome 5. This localization contradicts previous reports, based on genetic investigation of somatic cell hybrids, that placed the MHC on chromosome 2 of this species. In the chimpanzee, the MHC loci were localized to 5p21.3, corresponding precisely to their location on human chromosome 6p21.3. 相似文献
3.
Molecular and Biochemical Characterization of Three Anthocyanin Synthetic Enzymes from Gentiana triflora 总被引:5,自引:0,他引:5
Tanaka Yoshikazu; Yonekura Keiko; Fukuchi-Mizutani Masako; Fukui Yuko; Fujiwara Hiroyuki; Ashikari Toshihiko; Kusumi Takaaki 《Plant & cell physiology》1996,37(5):711-716
Full length cDNA clones of flavonoid 3',5'-hydroxylase, dihydroflavonol4-reductase and flavonoid 3-glucosyltransferase were clonedfrom petals of Gentiana triflora. Their sequences were homologousto counterparts from other plants. Flavonoid 3',5'-hydroxylaseand flavonoid 3-glucosyltransferase were enzymatically characterizedby expressing cDNAs in heterologous expression systems. (Received May 21, 1996; Accepted June 4, 1996) 相似文献
4.
M. Hakoda Naoyuki Kamatani Sakura Kurumada Yuko Hirai Kimitaka Sakamoto Hisashi Yamanaka Chihiro Terai Sadao Kashiwazaki 《Human genetics》1997,99(2):164-170
Both germline and somatic mutations are known to affect phenotypes of human cells in vivo. In previous studies, we cloned
mutant peripheral blood T cells from germline heterozygous humans for adenine phosphoribosyltransferase (APRT) (EC 2.4.2.7)
deficiency and found that approximately 1.3 × 10–4 peripheral T cells had undergone in vivo somatic mutations. Loss of heterozygosity (LOH) was the major cause of the mutations
at the APRT locus since approximately 80% of the mutant T cell clones exhibited loss of normal alleles. In the present study,
we identified three heterozygous individuals for APRT deficiency (representing two separate families), in whom none of the
somatic mutant cells exhibited LOH at the APRT locus. The germline mutant APRT alleles of these heterozygotes from two unrelated
families had the same gross DNA abnormalities detectable by Southern blotting. None of the germline mutant APRT alleles so
far reported had such gross DNA abnormalities. The data suggest that the germline mutation unique to these heterozygous individuals
is associated with the abrogation of LOH in somatic cells. The absence of LOH at a different locus has already been reported
in vitro in an established cell line but the present study describes the first such event in vivo in human individuals.
Received: 10 May 1996 相似文献
5.
6.
Shinsaku Tokuda Young Hak Kim Hisako Matsumoto Shigeo Muro Toyohiro Hirai Michiaki Mishima Mikio Furuse 《PloS one》2015,10(12)
The relationship between chronic inflammation and cancer is well known. The inflammation increases the permeability of blood vessels and consequently elevates pressure in the interstitial tissues. However, there have been only a few reports on the effects of hydrostatic pressure on cultured cells, and the relationship between elevated hydrostatic pressure and cell properties related to malignant tumors is less well understood. Therefore, we investigated the effects of hydrostatic pressure on the cultured epithelial cells seeded on permeable filters. Surprisingly, hydrostatic pressure from basal to apical side induced epithelial stratification in Madin-Darby canine kidney (MDCK) I and Caco-2 cells, and cavities with microvilli and tight junctions around their surfaces were formed within the multi-layered epithelia. The hydrostatic pressure gradient also promoted cell proliferation, suppressed cell apoptosis, and increased transepithelial ion permeability. The inhibition of protein kinase A (PKA) promoted epithelial stratification by the hydrostatic pressure whereas the activation of PKA led to suppressed epithelial stratification. These results indicate the role of the hydrostatic pressure gradient in the regulation of various epithelial cell functions. The findings in this study may provide clues for the development of a novel strategy for the treatment of the carcinoma. 相似文献
7.
Mitsuaki Yamashita Masafumi Kaneko Harukuni Tokuda Katsumi Nishimura Yuko Kumeda Akira Iida 《Bioorganic & medicinal chemistry》2009,17(17):6286-6291
A series of naphthoquinones based on the naphtho[2,3-b]furan-4,9-dione skeleton such as (−)-5-hydroxy-2-(1′-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (1) and its positional isomer, (−)-8-hydroxy-2-(1′-hydoxyethyl)naphtho[2,3-b]furan-4,9-dione (2), which are secondary metabolites found in the inner bark of Tabebuia avellanedae, were stereoselectively synthesized and their biological activities were evaluated in conjunction with those of their corresponding enantiomers. Compound 1 exhibited potent antiproliferative effect against several human tumor cell lines, but its effect against some human normal cell lines was much lower than that of mitomycin. On the other hand, its enantiomer (R)-1 was less active toward the above tumor cell lines than 1. The antiproliferative effect of 2 against all tumor cell lines was significantly reduced. These results indicated the presence of the phenolic hydroxy group at C-5 is of great important for increasing antiproliferative effect. In addition, 1 also showed higher cancer chemopreventive activity than 2, while there were no significant differences between 1 and 2 in antimicrobial activity. Both compounds displayed modest antifungal and antibacterial activity (Gram-positive bacteria), whereas they were inactive against Gram-negative bacteria. 相似文献
8.
9.
The site of production of meiosis-inducing substance (MIS), produced in the ovary under the influence of gonad-stimulating substance (GSS) taken from radial nerves, was studied with the starfish, Asterina pectinifera. The rate of oocyte maturation observed in isolated oocytes with follicles kept in sea water containing GSS (100 μg/ml) was generally low when a small number of eggs per unit quantity of sea water was used. However, with increased number of oocytes per milliliter of GSS-sea water, the maturation rate increased up to 100% (104 eggs/ml). The supernatant of such an incubation mixture of oocytes and GSS contained an appreciable amount of MIS. When a large number of oocytes (104/ml) was used, the rate of oocyte maturation increased with the rise in concentration of GSS. Isolated follicles were found to produce MIS when incubated in sea water containing GSS, suggesting that the site of production of MIS is the follicle cells. The physiological role of the follicle cells surrounding the full grown oocytes seems to be to produce MIS just before spawning under the influence of GSS. 相似文献
10.
Jaclyn S. Long Yuko Fujiwara Joanne Edwards Claire L. Tannahill Gabor Tigyi Susan Pyne Nigel J. Pyne 《The Journal of biological chemistry》2010,285(46):35957-35966
We demonstrate here that the bioactive lipid sphingosine 1-phosphate (S1P) uses sphingosine 1-phosphate receptor 4 (S1P4) and human epidermal growth factor receptor 2 (HER2) to stimulate the extracellular signal regulated protein kinase 1/2 (ERK-1/2) pathway in MDA-MB-453 cells. This was based on several lines of evidence. First, the S1P stimulation of ERK-1/2 was abolished by JTE013, which we show here is an S1P2/4 antagonist and reduced by siRNA knockdown of S1P4. Second, the S1P-stimulated activation of ERK-1/2 was almost completely abolished by a HER2 inhibitor (ErbB2 inhibitor II) and reduced by siRNA knockdown of HER2 expression. Third, phyto-S1P, which is an S1P4 agonist, stimulated ERK-1/2 activation in an S1P4- and HER2-dependent manner. Fourth, FTY720 phosphate, which is an agonist at S1P1,3,4,5 but not S1P2 stimulated activation of ERK-1/2. Fifth, S1P stimulated the tyrosine phosphorylation of HER2, which was reduced by JTE013. HER2 which is an orphan receptor tyrosine kinase is the preferred dimerization partner of the EGF receptor. However, EGF-stimulated activation of ERK-1/2 was not affected by siRNA knockdown of HER2 or by ErbB2 (epidermal growth factor receptor 2 (or HER2)) inhibitor II in MDA-MB-453 cells. Moreover, S1P-stimulated activation of ERK-1/2 does not require an EGF receptor. Thus, S1P and EGF function in a mutually exclusive manner. In conclusion, the magnitude of the signaling gain on the ERK-1/2 pathway produced in response to S1P can be increased by HER2 in MDA-MB-453 cells. The linkage of S1P with an oncogene suggests that S1P and specifically S1P4 may have an important role in breast cancer progression. 相似文献