全文获取类型
收费全文 | 1476篇 |
免费 | 86篇 |
国内免费 | 1篇 |
专业分类
1563篇 |
出版年
2022年 | 21篇 |
2021年 | 31篇 |
2020年 | 17篇 |
2019年 | 25篇 |
2018年 | 32篇 |
2017年 | 31篇 |
2016年 | 49篇 |
2015年 | 49篇 |
2014年 | 67篇 |
2013年 | 78篇 |
2012年 | 93篇 |
2011年 | 93篇 |
2010年 | 57篇 |
2009年 | 56篇 |
2008年 | 62篇 |
2007年 | 68篇 |
2006年 | 47篇 |
2005年 | 66篇 |
2004年 | 44篇 |
2003年 | 35篇 |
2002年 | 27篇 |
2001年 | 17篇 |
2000年 | 25篇 |
1999年 | 23篇 |
1997年 | 7篇 |
1993年 | 6篇 |
1992年 | 17篇 |
1991年 | 25篇 |
1990年 | 24篇 |
1989年 | 30篇 |
1988年 | 18篇 |
1987年 | 19篇 |
1986年 | 19篇 |
1985年 | 21篇 |
1984年 | 15篇 |
1983年 | 18篇 |
1982年 | 13篇 |
1981年 | 10篇 |
1980年 | 22篇 |
1979年 | 24篇 |
1978年 | 12篇 |
1977年 | 14篇 |
1976年 | 15篇 |
1975年 | 14篇 |
1974年 | 20篇 |
1973年 | 10篇 |
1972年 | 10篇 |
1971年 | 12篇 |
1970年 | 9篇 |
1969年 | 9篇 |
排序方式: 共有1563条查询结果,搜索用时 15 毫秒
31.
The role of microtubules in platelet aggregation and secretion has been analyzed using platelets permeabilized with digitonin and monoclonal antibodies to alpha (DM1A) and beta (DM1B) subunits of tubulin. Permeabilized platelets were able to undergo aggregation and secretory release. However, threshold doses of agonists capable of eliciting a second wave of aggregation and the platelet release reaction were higher than in control platelets exposed to dimethyl sulfoxide, the solvent for digitonin. Both antibodies to alpha and beta tubulin caused a further increase in the threshold concentration of agonists and inhibited the secretory release of permeabilized platelets, but were ineffective using intact platelets. Neither monoclonal antibody inhibited polymerization or depolymerization of platelet tubulin in vitro. Antibodies to platelet actin and myosin also exhibited an inhibitory activity on platelet aggregation albeit less severe than that observed with the antibodies to alpha and beta tubulin. There was evidence of an interaction between DM1A and DM1B and the antibodies to actin and myosin. The interaction of platelet tubulin and myosin was investigated by two different methods. (1) Coprecipitation of the proteins at low ionic strength at which tubulin by itself did not precipitate and (2) affinity chromatography on columns of immobilized myosin. Tubulin freed of its associated proteins (MAPs) by phosphocellulose chromatography bound to myosin in a molar ratio which approached 2. Platelet actin competed with tubulin for 1 binding site on the myosin molecule. MAPs also reduced the binding stoichiometry of tubulin/myosin. Treatment of microtubule protein with p-chloromercuribenzoate or colchicine did not influence its binding to myosin. DM1A and DM1B inhibited the interaction of tubulin and myosin. This effect could also be demonstrated by reaction of electrophoretic transblots of extracted platelet tubulin with the respective proteins. We interpret these results as evidence for an interference of the two monoclonal antibodies to the tubulin subunits (DM1A and DM1B) with the translocation of microtubule protein from its submembranous site to a more central one during the activation process. 相似文献
32.
33.
David D. Stenehjem Michael Toole Joseph Merriman Kinjal Parikh Stephanie Daignault Sarah Scarlett Peg Esper Katherine Skinner Aaron Udager Srinivas Kiran Tantravahi David Gill Alli M. Straubhar Archana M. Agarwal Kenneth F. Grossmann Wolfram E. Samlowski Bruce Redman Neeraj Agarwal Ajjai Alva 《Cancer immunology, immunotherapy : CII》2016,65(8):941-949
34.
A A Pollice J P McCoy S E Shackney C A Smith J Agarwal D R Burholt L E Janocko F J Hornicek S G Singh R J Hartsock 《Cytometry》1992,13(4):432-444
A cell fixation and permeabilization procedure consisting of sequential paraformaldehyde and methanol was evaluated and found suitable for concomitant flow cytometric quantification of total cellular DNA, immunofluorescence measurements of cell surface proteins, and immunofluorescence measurements of intracellular proteins. Paraformaldehyde/methanol-fixed cells exhibited significantly greater intracellular antitubulin immunofluorescence than cells fixed with paraformaldehyde or methanol alone (p less than 0.002) and significantly greater intracellular antitubulin immunofluorescence than cells fixed with methanol followed by paraformaldehyde (p less than 0.006). With paraformaldehyde/methanol fixation, cell morphology was well preserved and forward and right angle light scatter properties were sufficiently well maintained to permit gating on these parameters. Cell surface marker staining with fluorescent anti-leukocyte antibodies was unaffected by fixation with paraformaldehyde/methanol. Paraformaldehyde effects on the intensity of DNA staining with propidium iodide were dependent on paraformaldehyde concentration and fixation temperature; these effects were least pronounced at low paraformaldehyde concentrations (0.25% or less), and at temperatures lower than 37 degrees C. Paraformaldehyde fixation may result in differences in propidium iodide staining of DNA in some diploid cells, which may produce small spurious aneuploid peaks in normal peripheral blood leukocytes. Paraformaldehyde fixation also produces an apparent increase in the DNA index of aneuploid cell populations in comparison with methanol fixation, particularly when the DNA index exceeds 1.5. Occasionally, this paraformaldehyde fixation-induced effect is useful in identifying biologically distinct near-diploid subpopulations in tumors. 相似文献
35.
The implications of the methylene tetrahydrofolate reductase (MTHFR) gene and the level of homocysteine in the pathogenesis of coronary artery disease (CAD) have been extensively studied in various ethnic groups. Our aim was to discover the association of MTHFR (C677T) polymorphism and homocysteine level with CAD in north Indian subjects. The study group consisted of 329 angiographically proven CAD patients, and 331 age and sex matched healthy individuals as controls. MTHFR (C677T) gene polymorphism was detected based on the polymerase chain reaction and restriction digestion with HinfI. Total homocysteine plasma concentration was measured using immunoassay. T allele frequency was found to be significantly higher in patients than in the control group. We found significantly elevated levels of mean homocysteine in the patient group when compared to the control group (p = 0.00). Traditional risk factors such as diabetes, hypertension, smoking habits, a positive family history and lipid profiles (triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol), were found significantly associated through univariate analysis. Furthermore, multivariable logistics regression analysis revealed that CAD is significantly and variably associated with diabetes, hypertension, smoking, triglycerides and HDL-cholesterol. Our findings showed that MTHFR C677T polymorphism and homocysteine levels were associated with coronary artery disease in the selected population. 相似文献
36.
Nordihydroguaiaretic acid (NDGA), which occurs in the resinous exudates of many plants is used as an antioxidant in fats and oils. In this study we show that NDGA inhibited the mutagenicity of methyl methanesulfonate, benzo[a]pyrene (BP), 2-aminofluorene, and aflatoxin B1 in Salmonella typhimurium strain TA100 or TA98 in the absence and presence of rat hepatic microsomal activation system. The addition of NDGA during and after nitrosation of methylurea (MU) resulted in a dose-dependent inhibition of mutagenicity induced by nitrosation products of MU. In a two-stage skin tumorigenesis protocol using 7,12-dimethylbenz[a]anthracene (DMBA) as the initiating agent followed by twice weekly applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) as tumor promoter, pretreatment of animals with NDGA prior to DMBA application, afforded significant protection against skin tumorigenicity in female SENCAR mice. In additional studies, skin application of NDGA also inhibited the binding of topically applied [3H]BP and [3H]DMBA to epidermal DNA. When assessed in the anti-tumor promotion protocol, pretreatment of animals with NDGA before each application of TPA in DMBA-initiated mouse skin, resulted in 72% decrease in the total number of tumors when compared to non-NDGA pretreated animals. The possible mechanism(s) of the antimutagenic and anti-tumorigenic activities may be due to the multiple effects of NDGA as inhibitor of the carcinogen metabolism and DNA-adduct formation, scavenger of carcinogen free radicals, and as inhibitor of TPA-induced ornithine decarboxylase activity. 相似文献
37.
Gupta Saurabh Chaubey Kundan Kumar Agarwal Prabhat Kuenstner J. Todd Parashar Deepak Singh Shoor Vir 《Molecular biology reports》2021,48(10):7013-7020
Molecular Biology Reports - A 26-year-old male had a history of frequent bowel movements, mushy stool with mucus and loss of 25 kg body weight in 6 months was diagnosed as a case... 相似文献
38.
Deschner J Wypasek E Ferretti M Rath B Anghelina M Agarwal S 《Journal of biomechanics》2006,39(10):1796-1803
OBJECTIVE: We sought to determine whether fibrochondrocytes from menisci express receptor activator of NF-kappaB (RANK), its ligand (RANKL), or osteoprotegerin (OPG) and, if so, whether their expression is modulated by dynamic mechanical loading under inflammatory and normal conditions. METHODS: Fibrochondrocytes from rat menisci were subjected to cyclic tensile strain (CTS) at various magnitudes and frequencies in the presence or absence of interleukin (IL)-1beta for up to 24 h. In order to determine whether a possible regulatory effect of mechanical loading on RANKL and its receptors under inflamed conditions is sustained, cells were stimulated with IL-1beta for 24 h while being subjected to CTS only for the initial 4 and 8h, respectively. Regulation of RANKL, RANK, and OPG expression and synthesis were determined by semiquantitative and real-time PCR, Western blotting, and immunofluorescence. RESULT: Fibrochondrocytes constitutively expressed low levels of RANKL and RANK but marked levels of OPG. IL-1beta upregulated expression and synthesis of RANKL and RANK significantly (p<0.05), whereas expression of OPG was unaffected following 4 and 24 h. When fibrochondrocytes were simultaneously subjected to CTS and IL-1beta, expression of RANKL and RANK was significantly (p<0.05) downregulated as compared to that of IL-1beta-stimulated unstretched cells. The inhibitory effect of CTS on the IL-1beta-induced upregulation of RANKL and RANK was sustained as well as magnitude and frequency dependent. CONCLUSIONS: Our study provides evidence that RANKL and its receptors are expressed in fibrochondrocytes from meniscus. These data also demonstrate that dynamic mechanical loading can modify the expression of RANKL and RANK in inflammatory conditions. 相似文献
39.
Diethylcarbamazine (DEC) reacted with liver cell plasma membrane of rodent hosts-cotton rat, albino rat and Mastomys natalensis exhibiting the presence of both saturable and unsaturable components. The presence of lectins or sugar derivatives did not affect the binding significantly. The drug showed similar binding pattern with serum but the saturation was reached at a much lower concentration of the ligand. Data obtained with a variety of macromolecules, particularly with the homopolymers of amino acids indicate that DEC does not require any specific constituent of the membrane for binding. The nonspecific nature of DEC binding does not provide any convincing clue for the accumulation of microfilariae specifically in the liver following the drug treatment. 相似文献
40.
Surjit Singh Gernot Fritze Bingliang Fang Shoji Harada Yong K. Paik Rolf Eckey Dharam P. Agarwal H. Werner Goedde 《Human genetics》1989,83(2):119-121
Summary Genotyping of mitochondrial aldehyde dehydrogenase (ALDH I) was performed in enzymatically amplified DNA of 20 Chinese, Japanese and South Korean families (85 individuals) and in 113 unrelated persons by employing allele-specific oligonucleotide probes and dot blot hybridization. Genotyping individuals with phenotypic deficiency of ALDH I activity always showed the presence of at least one mutant allele. The data are compatible with a model assuming dominant inheritance of the mutant allele, which we have previously suggested on the basis of a population study. 相似文献