全文获取类型
收费全文 | 2098篇 |
免费 | 100篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 4篇 |
2021年 | 22篇 |
2020年 | 15篇 |
2019年 | 21篇 |
2018年 | 37篇 |
2017年 | 37篇 |
2016年 | 62篇 |
2015年 | 87篇 |
2014年 | 85篇 |
2013年 | 172篇 |
2012年 | 153篇 |
2011年 | 141篇 |
2010年 | 111篇 |
2009年 | 93篇 |
2008年 | 144篇 |
2007年 | 153篇 |
2006年 | 140篇 |
2005年 | 141篇 |
2004年 | 95篇 |
2003年 | 103篇 |
2002年 | 89篇 |
2001年 | 13篇 |
2000年 | 20篇 |
1999年 | 21篇 |
1998年 | 23篇 |
1997年 | 16篇 |
1996年 | 23篇 |
1995年 | 20篇 |
1994年 | 6篇 |
1993年 | 8篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 7篇 |
1989年 | 10篇 |
1988年 | 8篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 13篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 12篇 |
1981年 | 4篇 |
1980年 | 9篇 |
1978年 | 4篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1975年 | 5篇 |
1974年 | 6篇 |
1973年 | 4篇 |
排序方式: 共有2199条查询结果,搜索用时 31 毫秒
121.
122.
123.
Laminin-alpha5 chain was localized in all epithelial basement membranes (BMs) of mouse submandibular gland (SMG) from the onset of branching morphogenesis and became restricted to BMs of epithelial ducts in the adult. To investigate whether the laminin-alpha5 chain plays a role in branching morphogenesis, a set of cell-adhesive peptides from the C-terminal globular domains (LG1-5) was tested for their effects in SMG organ cultures. One peptide, LVLFLNHGH (A5G77f), which represents a sequence located in the connecting loop between strands E and F of LG4, perturbed branching morphogenesis and resulted in irregularities in the contours of epithelial structures, with formation of deep clefts. The data suggest a role for the laminin-alpha5 LG4 module in the development of the duct system, rather than in the bifurcation of epithelial clusters. The epithelial BM of A5G77f-peptide-treated explants was continuous, which was in contrast to our previous finding of impaired epithelial BM assembly in explants treated with the laminin-alpha1 LG4 module peptide, or with a monoclonal antibody against this domain. A5G77f also perturbed in vitro development of lung and kidney. These results suggest a crucial role for the LG4 module of laminin-alpha5 in epithelial morphogenesis that is distinct from that of the laminin-alpha1 LG4. 相似文献
124.
Firefly luciferase can catalyze the formation of fatty acyl-CoA via fatty acyl-adenylate from fatty acid in the presence of ATP, Mg2+ and coenzyme A (CoA). A long chain fatty acyl-CoA (C16–C20), produced by luciferase from a North American firefly (Photinus pyralis) and a Japanese firefly (Luciola cruciata), was isolated and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis. Of a number of substrates tested, linolenic acid (C18:3) and arachidonic acid (C20:4) appear to be suitable for acyl-CoA synthesis. This evidence suggests that firefly luciferase within peroxisomes of the cells in the photogenic organ may be a bifunctional enzyme, catalyzing not only the bioluminescence reaction but also the fatty acyl-CoA synthetic reaction. 相似文献
125.
Jesmin S Hattori Y Sakuma I Mowa CN Kitabatake A 《American journal of physiology. Heart and circulatory physiology》2002,283(4):H1387-H1397
With the use of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of human non-insulin-dependent diabetes mellitus (NIDDM), we assessed whether ANG II is involved in coronary capillary angiogenesis at the insulin-resistant stage of NIDDM (20 wk of age). In OLETF rats, ANG II labeling and angiotensin type 1 (AT(1)) receptor expression in coronary vessels were increased more than in nondiabetic controls. A marked increase in vascular expression of vascular endothelial growth factor (VEGF) at both mRNA and protein levels was found in OLETF rats. The increased expression level of VEGF was associated with accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) activated by increased advanced glycation end products (AGEs). Morphometric analysis showed a significantly increased total coronary capillary density, which was a result of arterialization of the venular capillary portion in OLETF rats. Treatment of OLETF rats with candesartan, an AT(1) receptor blocker, inhibited vascular expressions of VEGF, HIF-1alpha, and AGEs, and ameliorated the morphometric changes. These results suggest a key role of ANG II in the pathogenesis of the coronary capillary remodeling in this NIDDM model. 相似文献
126.
Tada Y O-Wang J Takiguchi Y Tatsumi K Kuriyama T Okada S Tokuhisa T Sakiyama S Tagawa M 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(5):2241-2245
Fas ligand (FasL)-expressing tumor cells are found to effectively mediate rejection of the coinoculated FasL negative parental cells while having no effect on the growth of histologically distinct tumor cells. These observations indicate that FasL induces a specific immune response against Ag derived from FasL-bearing tumors and suggest a possible role for FasL in tumor Ag presentation. Indeed, tumor cells expressing FasL can efficiently interact with dendritic cells (DCs) and this interaction requires the expression of membrane-bound FasL on tumors and Fas on DCs. Moreover, DCs cocultured with FasL-expressing tumors are able to elicit a tumor-specific immune response in vivo, suggesting that DCs acquire tumor Ag during the Fas/FasL-mediated DC-tumor contact. These results identify a novel role for FasL in augmenting tumor-DC interactions and subsequent tumor Ag acquisition by DCs, and suggest that FasL-expressing tumor cells could be used to generate tumor-specific DC vaccines. 相似文献
127.
Hashimoto Y Ito Y Arakawa E Kita Y Terashita K Niikura T Nishimoto I 《Journal of neurochemistry》2002,80(3):426-437
While it has been reported that familial Alzheimer's disease (FAD)-linked mutants of amyloid precursor protein (APP) and presenilin (PS)2 induce neuronal cytotoxicity in a manner sensitive to antioxidant and pertussis toxin (PTX), little of the mechanism for PS1-mediated neuronal cell death has been characterized. We previously found that multiple mechanisms, different in detail, underlie cytotoxicities by two FAD-linked mutants of APP, using neuronal cells with an ecdysone-controlled expression system. Here we report that this system revealed that (i) low expression of FAD-linked M146L-PS1 caused neuronal cell death, whereas that of wild-type (wt)PS1 did not; (ii) mutation-specific cytotoxicity by M146L-PS1 was sensitive to antioxidant glutathione-ethyl-ester and resistant to Ac-DEVD-CHO; (iii) cytotoxicity by higher expression of wtPS1 was resistant to both; and (iv) cytotoxicity by M146L-PS1 was inhibited by PTX. It was also highly likely that the involved superoxide-generating enzyme was nitric oxide synthase (NOS), and that the PTX-sensitive cytotoxic signal by M146L-PS1 was mediated by none of the G(i/o) proteins. We conclude that M146L-PS1 activates a NOS-mediated cytotoxic pathway via a novel PTX target. 相似文献
128.
Apolipoprotein E and H polymorphisms in Mongolian Buryat: allele frequencies and relationship with plasma lipid levels 总被引:1,自引:0,他引:1
Tsunoda K Harihara S Dashnyam B Semjidmaa D Yamaguchi Y Tanabe Y Sakai N Sato A Sato K 《Human biology; an international record of research》2002,74(5):659-671
A Buryat population consisting of seven tribal groups in eastern Mongolia has been screened to determine the frequency distribution of different apolipoprotein E and H alleles (APOE and APOH, genes) coding for common isoforms and their association with quantitative plasma lipid levels. Allele frequencies at the APOE locus in 125 healthy Buryat aged 17 to 73 years were highest for APOE*3 (0.804), followed by APOE*4 (0.164) and APOE*2 (0.032). The APOH locus had high frequencies of APOH*2 (0.912) and APOH*3 (0.088). APOH*1 was not detected. No significant differences were observed in the overall APOE allele frequencies between the Buryat and the Siberian Evenki, Inuits, and Indians in Asia, or with some European whites. The frequency distribution of the overall APOH alleles of the Buryat was similar to that of the Japanese in Asia. Overall plasma lipid levels of the Buryat (males aged 20 to 73 years, females aged 21 to 64 years) were considerably lower, comparable to those of the Evenki. The APOE*4/E*3 males had significantly high total- and LDL-cholesterol levels compared with the APOE*3/E*3 males (p < 0.025 and p < 0.01, respectively). No significant effects of the APOH genotypes on any of the plasma lipid levels were observed. In particular, our data regarding APOE suggest that the Buryat are genetically close in allele frequencies to the Evenki and Inuits, but differ from them in the association of genotype APOE*4/E*3 with cholesterol levels. 相似文献
129.
In a metabolic study of [1-(14)C]geranylgeranial involving rat thymocytes, the radioactivity was mainly incorporated into two metabolites, Z1 and Z2, the latter moving slower than the former on a silica-gel thin-layer plate. The time course of Z1 and Z2 formation superficially suggested a precursor-product relationship between Z1 and Z2. The two metabolites were chemically converted to their methyl esters on treatment with trimethylsilyl diazomethane. Z1 was cochromatographed with E,E,E-geranylgeranoic acid (GGA). Z2 was prepared in a large quantity from geranylgeranial using thymocytes, and purified by TLC followed by ESI (negative ion mode) or EI mass-spectrometry. The observation of a negative ion at m/z 305 on ESI and a molecular ion at m/z 306 (C(20)H(34)O(2)) with fragments similar to GGA on EI implied that Z2 was dihydroGGA, which has been detected in the urine and serum of patients with Refsum disease. The EI mass spectrum of (R)-2,3-dihydroGGA was identical to that of Z2. The diastereomeric amide synthesized from metabolite Z2 with (R)-1-(1-naphtyl)ethylamine was cochromatographed with (R acid, R) amide, not with (S acid, R) amide, which were similarly synthesized from (R)- and (S)-2,3-dihydroGGAs, respectively. In another metabolic study on [1-(14)C]geranylgeraniol (GGOH), the radioactivity was similarly incorporated into a metabolite corresponding to (R)-2,3-dihydroGGA. (R)-2,3-DihydroGGA induced DNA ladder formation with a maximum at 15 mciroM in thymocytes. However, 2,3-dihydrofarnesoic acid did not induce it at all. 相似文献
130.
We have been studying a lysozyme derivative, called mPEG-lysozyme, in which Lys 33 is bound with a monomethoxypolyethylene glycol derivative. Here, we examined the surface hydrophobicity of the derivative and also its interactions with lipopolysaccharides and lipid bilayers. These properties may affect the antimicrobial activity of mPEG-lysozyme toward Gram-negative microorganisms. The lysozyme derivative had more than 150% of the antimicrobial activity for such microorganisms with that of native lysozyme taken to be 100%. Spectroscopic analyses indicated that mPEG-lysozyme bound to lipopolysaccharides with higher affinity than lysozyme, because of the high surface hydrophobicity of the derivative. In an experiment on carboxyfluorescein-leakage, mPEG-lysozyme strongly interacted with liposomes constructed from phosphatidylcholine, releasing carboxyfluorescein from the liposomes more effectively than lysozyme did. mPEG-lysozyme may perturb the outer membrane of Gram-negative microorganisms, gaining itself access to the peptidoglycan layers of the bacterium. 相似文献