全文获取类型
收费全文 | 361篇 |
免费 | 34篇 |
出版年
2022年 | 4篇 |
2021年 | 4篇 |
2020年 | 8篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 7篇 |
2015年 | 14篇 |
2014年 | 12篇 |
2013年 | 25篇 |
2012年 | 22篇 |
2011年 | 19篇 |
2010年 | 15篇 |
2009年 | 11篇 |
2008年 | 20篇 |
2007年 | 22篇 |
2006年 | 15篇 |
2005年 | 15篇 |
2004年 | 13篇 |
2003年 | 15篇 |
2002年 | 9篇 |
2001年 | 14篇 |
2000年 | 12篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1997年 | 7篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1969年 | 2篇 |
1968年 | 7篇 |
1967年 | 1篇 |
排序方式: 共有395条查询结果,搜索用时 15 毫秒
101.
25,26-dihydroxyvitamin D3 is not a major intermediate in 25-hydroxyvitamin D3-26,23-lactone formation 总被引:1,自引:0,他引:1
Structural similarities between 25S,26-dihydroxyvitamin D3 and 25-hydroxyvitamin D3-26,23-lactone and their concomitant multifold increase in the plasma of animals treated with pharmacological doses of vitamin D3 suggest a precursor-product relationship. However, a single dose of 25S,26-[3H]dihydroxyvitamin D3 given to rats treated chronically with pharmacological amounts of vitamin D3 did not result in detectable plasma 25-[3H]hydroxyvitamin D3-26,23-lactone. Multiple doses of synthetic 25S,26-dihydroxyvitamin D3 given to vitamin D3-deficient rats treated chronically with pharmacological amounts of vitamin D2 also did not result in detectable plasma 25-hydroxyvitamin D3-26,23-lactone. Furthermore, homogenates prepared from vitamin d-deficient chickens, dosed with 1,25-dihydroxyvitamin D3, converted 25-[3H]hydroxyvitamin D3 to 25-[3H]hydroxyvitamin D3-26,23-lactone. But these same homogenates did not convert 25S,26-[3H]dihydroxyvitamin D3 to 25-[3H]hydroxyvitamin D3-26,23-lactone. These data indicate that 25,26-dihydroxyvitamin D3 is not an intermediate in 25-hydroxyvitamin D326, 23-lactone formation. 相似文献
102.
103.
D'Onofrio J Erra E Di Fabio G Iadonisi A Petraccone L De Napoli L Barone G Balzarini J Giancola C Montesarchio D 《Nucleosides, nucleotides & nucleic acids》2007,26(10-12):1225-1229
A number of 5'-and 3'-glycoconjugates of the oligonucleotide (5')d(TGGGAG)(3') have been synthesized, exploiting fully automated, online phosphoramidite-based solid phase strategy, as potential anti-HIV-1 agents. The thermodynamic stability of the resulting quadruplexes has been investigated by thermal denaturation studies, via a detailed CD Q1 analysis. 相似文献
104.
C Allard V Desgagné J Patenaude M Lacroix L Guillemette MC Battista M Doyon J Ménard JL Ardilouze P Perron L Bouchard MF Hivert 《Epigenetics》2015,10(4):342-351
Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS10) and showed it was an adequate instrumental variable (β = 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE = 0.007; P = 7.8 × 10−11; N = 467). A higher GRS10 was associated with lower methylation levels at cg12083122 located near LEP (β = −0.072 unit per additional risk allele; SE = 0.04; P = 0.05; N = 166). Direction and effect size of association between the instrumental variable GRS10 and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (β = −0.17 log of cord blood leptin per unit; SE = 0.07; P = 0.01; N = 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation. 相似文献
105.
de Nigris F Rienzo M Sessa M Infante T Cesario E Ignarro LJ Al-Omran M Giordano A Palinski W Napoli C 《Journal of cellular physiology》2012,227(11):3639-3647
Oxidation and glycation enhance foam cell formation via MAPK/JNK in euglycemic and diabetic subjects. Here, we investigated the effects of glycated and oxidized LDL (glc-oxLDL) on MAPK-ERK and JNK signaling pathways using human coronary smooth muscle cells. Glc-oxLDL induced a broad cascade of MAPK/JNK-dependent signaling transduction pathways and the AP-1 complex. In glc-oxLDL treated coronary arterioles, tumor necrosis factor (TNF) α increased JNK phosphorylation, whereas protein kinase inhibitor dimethylaminopurine (DMAP) prevented the TNF-induced increase in JNK phosphorylation. The role of MKK4 and JNK were then investigated in vivo, using apolipoprotein E knockout (ApoE(-/-)) mice. Peritoneal macrophages, isolated from spontaneously hyperlipidemic but euglycemic mice showed increases in both proteins and phosphorylated proteins. Compared to streptozotocin-treated diabetic C57BL6 and nondiabetic C57BL6 Wt mice, in streptozotocin-diabetic ApoE(-/-) mice, the increment of foam cell formation corresponded to an increment of phosphorylation of JNK1, JNK2, and MMK4. Thus, we provide a first line of evidence that MAPK-ERK/JNK pathways are involved in vascular damage induced by glycoxidation. 相似文献
106.
107.
108.
Jason W. Locasale Andrew A. Napoli Shengfeng Chen Helen M. Berman 《Journal of molecular biology》2009,386(4):1054-696
One obstacle to achieving complete understanding of the principles underlying sequence-dependent recognition of DNA is the paucity of structural data for DNA recognition sequences in their free (unbound) state. Here, we carried out crystallization screening of 50 DNA duplexes containing cognate protein binding sites and obtained new crystal structures of free DNA binding sites for three distinct modes of DNA recognition: anti-parallel β strands (MetR), helix-turn-helix motif + hinge helices (PurR), and zinc fingers (Zif268). Structural changes between free and protein-bound DNA are manifested differently in each case. The new DNA structures reveal that distinctive sequence-dependent DNA geometry dominates recognition by MetR, protein-induced bending of DNA dictates recognition by PurR, and deformability of DNA along the A-B continuum is important in recognition by Zif268. Together, our findings show that crystal structures of free DNA binding sites provide new information about the nature of protein-DNA interactions and thus lend insights towards a structural code for DNA recognition. 相似文献
109.
Veronica M. Cóceres Melina Laguia Becher Maximiliano G. De Napoli Marina Clemente 《Experimental parasitology》2010,126(2):263-266
Recombinant Toxoplasma gondii small heat shock protein HSP20, surface antigen SAG1 and dense granule GRA7 were analyzed by IgG-ELISA with serum samples of Toxoplasma infected humans grouped as I (IgG+, IgM+), II (IgG+, IgM−) and III (IgG−, IgM−). rHSP20 reacted against 80% and 62.5% of serum samples from groups I and II, respectively. rSAG1 was recognized by 85% of the samples from group I and 70.8% from group II, whereas rGRA7 was recognized by 85% and 66.6% of the serum samples from groups I and II, respectively. When a combination of two or three recombinant antigens was used, the sensitivity values improved to 85-95% for group I and 87.5-91.7% for group II. All combinations tested produced similar reactivity profiles. None of the recombinant proteins reacted against group III serum samples. In conclusion, we demonstrated that T. gondii HSP20 elicits an important B-cell response during human infection, and could be suitable for the development of serodiagnosis tools. 相似文献
110.
EM Tazi I Lalya MF Tazi Y Ahellal H M'rabti H Errihani 《World journal of surgical oncology》2010,8(1):1-3
Goblet cell carcinoid of the large intestine is a rare neoplasm, usually located in ascending colon and rectum. A 60-year-old male patient underwent surgery after the diagnosis of acute abdomen. Exploratory laparotomy revealed perforation with a diameter of 1 cm at the site of the previously performed gastroenterostomy and dilatation of the right colic flexure, secondary to a solid obstructive mass located in the mid-portion of transverse colon. Histopathological investigation of the biopsies, taken from the gastroenterostomy site and the tumor, revealed mixed carcinoid-adenocarcinoma with carcinoid component, predominantly composed of goblet cells. Three cycles of FOLFOX-4 protocol was administered. Following respiratory distress secondary to pulmonary metastasis, the patient's condition deteriorated and subsequently died in the fourth postoperative month. Our aim with this paper is to point out that more cases should be reported for more effective diagnosis, histopathological study, clinical investigation, treatment and prognosis of this specific neoplasm. 相似文献