全文获取类型
收费全文 | 510篇 |
免费 | 38篇 |
专业分类
548篇 |
出版年
2022年 | 5篇 |
2021年 | 15篇 |
2020年 | 4篇 |
2018年 | 8篇 |
2017年 | 6篇 |
2016年 | 12篇 |
2015年 | 20篇 |
2014年 | 22篇 |
2013年 | 19篇 |
2012年 | 25篇 |
2011年 | 15篇 |
2010年 | 16篇 |
2009年 | 12篇 |
2008年 | 26篇 |
2007年 | 29篇 |
2006年 | 15篇 |
2005年 | 21篇 |
2004年 | 22篇 |
2003年 | 9篇 |
2002年 | 12篇 |
2001年 | 11篇 |
2000年 | 11篇 |
1999年 | 15篇 |
1998年 | 4篇 |
1997年 | 8篇 |
1996年 | 4篇 |
1995年 | 6篇 |
1993年 | 7篇 |
1992年 | 15篇 |
1991年 | 10篇 |
1990年 | 14篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 8篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1982年 | 4篇 |
1981年 | 20篇 |
1980年 | 7篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1976年 | 6篇 |
1975年 | 5篇 |
1973年 | 3篇 |
1972年 | 5篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1969年 | 3篇 |
1968年 | 6篇 |
排序方式: 共有548条查询结果,搜索用时 15 毫秒
1.
In order to investigate gene expression changes associated with cytotoxicity, we used cDNA arrays to monitor the expression
of over 5,000 genes in response to toxic stress in the HepG2 liver cell line. Cells were treated with cytotoxic doses of acetaminophen,
caffeine or thioacetamide for nine time points ranging from 1 to 24 h. Samples of mRNA from each time point were used to prepare
radiolabeled cDNA, which was hybridized to nylon-membrane-based cDNA arrays. High-stringency washes were applied to reduce
cross-hybridization. Analysis of spot intensities revealed that each compound led to approximately 150-250 gene expression
changes that were sustained over at least three adjacent time points. The affected genes could be classified into clusters
based on their temporal patterns of differential expression. A common set of 44 genes showed similar expression changes in
response to all three compounds. Of these changes, 90% could be confirmed by quantitative RT-PCR analysis. The results indicate
that detailed array-based time-course studies, coupled with a sensitive and highly specific confirmation assay, provide a
powerful means of identifying cytotoxicity-associated gene expression changes.
Electronic Publication 相似文献
2.
A study of GDP binding to purified thermogenin protein from brown adipose tissue. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
1. The binding of GDP to purified thermogenin protein was studied by using fluorescence spectroscopy and equilibrium dialysis. 2. GDP binding to thermogenin diminished fluorescence emission in a concentration-dependent manner that exhibited saturation. 3. Kd values for binding of nucleoside di- and tri-phosphates were lower than those for nucleoside monophosphates. 4. The GDP-induced fluorescence quenching was decreased by increasing pH, but the apparent Kd was unaltered by pH changes. 5. Equilibrium dialysis showed a Kd change from 3 to 6 microM when the pH was increased from 6.6 to 8.5. 6. The apparent pK of the fluorescence changes induced by pH (8.3) was identical with the apparent pK of the GDP-binding response. 7. The data are consistent with the existence of protonated and non-protonated forms of thermogenin protein that both bind GDP. 相似文献
3.
4.
C. J. Gore G. C. Scroop J. D. Marker P. G. Catcheside 《European journal of applied physiology and occupational physiology》1992,65(4):302-310
While haemoconcentration due to loss of plasma volume is well established during cycling, the existence of similar changes during running remains contentious. This study compared the changes in plasma volume and associated blood indices during 60 min of running and cycling at the same relative intensity (approximately 65% VO2max), with all changes referenced to blood indices obtained after 30 min seated at rest on a cycle ergometer. Plasma osmolarity increased similarly with both forms of exercise but was less than predicted for water loss alone, such that there was a net loss of sodium during exercise and of potassium postexercise, with essentially no loss of protein. Plasma volume decreased similarly (approximately 6.5%) in both exercise trials, but while that with cycling was initiated by exercise itself and was essentially maximal within 5 min, the reduction in plasma volume in the running trial was induced by adopting the upright posture and was complete before exercise began. These data would indicate that different mechanisms are responsible for the changes in plasma volume induced by running and cycling, while the similarity of change would suggest that there is a lower limit to any reduction in plasma volume, regardless of mechanism. Furthermore, the observation that the changes in plasma volume were complete before or early in exercise, would imply that oral water ingestion during prolonged exercise, which is essential for thermoregulation, may be more concerned with homeostasis of extravascular water rather than plasma volume. 相似文献
5.
Fine needle aspiration biopsy of metastatic melanoma. A morphologic analysis of 174 cases 总被引:1,自引:0,他引:1
The prognostic and therapeutic decisions in cases of metastatic melanoma depend upon the morphologic documentation of metastatic disease, which may rapidly and accurately be done by fine needle aspiration (FNA) biopsy of clinically suspicious lesions. The tumor cells derived from malignant melanomas demonstrate a wide range of appearances, however, and other neoplasms may be mimicked. Furthermore, additional neoplasms of other types are more frequent in melanoma patients: the possibility of a new primary tumor must be considered if the morphology of the tumor cells is uncharacteristic. Therefore, a study was undertaken to analyze the morphologic changes seen in FNA biopsy specimens from metastatic malignant melanoma and to determine which features could be the most useful in establishing a definitive diagnosis. A total of 174 consecutive cases, comprising 151 malignant aspirates and 23 inconclusive aspirates, were reviewed. The most significant features for identification of melanoma over other tumor types were the cell shape and nuclear position, the presence of numerous isolated neoplastic cells and occasional binucleated or multinucleated cells. Intracellular melanin in neoplastic cells was diagnostic when present, but it was absent in 60% of the cases. Macronucleoli and/or intranuclear cytoplasmic invaginations were characteristic but variable features. Morphology was also found to vary by site and cell type. Lung aspirates were less cellular and more likely to contain melanin. Aspirates of subcutaneous nodules were more often composed of spindle-shaped cells or of other variant cell types. Lymph node aspirates more often yielded epithelioid cells with macronucleoli and/or intranuclear invaginations. Spindle-cell melanomas usually demonstrated inconspicuous nuclei and rarely showed enlarged nucleoli. Epithelioid-cell tumors contained multinucleated cells and areas of cell wrapping more frequently than did spindle-cell tumors. The findings in this study emphasize that a full awareness of the spectrum of morphologic presentations of metastatic melanoma as well as of the clinical history are needed for greater precision in its diagnosis and for avoidance of the pitfall of misdiagnosing nonmelanomas with similar appearances. 相似文献
6.
William L. Daniel Berthie M. Ruoff D. Bruce Thompson Julius B. Gore 《Biochemical genetics》1985,23(9-10):771-786
Arylsulfatase B (arylsulfate sulfohydrolase; EC 3.1.6.1) activities in C57BL/6J, SWR/J, and A/J mouse liver approximate a 5:3:1 ratio. Each enzyme was purified to apparent homogeneity, and the properties of the three purified enzymes were compared. The purified enzyme behaved as a monomer with an apparent molecular weight of 50,000. The purified enzyme catalyzed the hydrolysis of p-nitrocatechol sulfate (pNCS), 4-methylumbelliferyl sulfate (4MUS), and chondroitin-4-sulfate (C4S) heptasaccharide. Purified SWR/J arylsulfatase B possessed a higher relative electrophoretic mobility at pH 4.0 than the A/J and C57BL/6J isozymes, and the SWR/J enzyme was more thermostable than either the C57BL/6J or the A/J enzyme. No differences were observed among the three enzymes with respect to their Michaelis constants for 4MUS and pNCS, isoelectric points, responses to inhibitors, pH optima, or electrophoretic mobilities at pH 8.3. The relative in vivo rates of synthesis of C57BL/6J, A/J, and SWR/J arylsulfatase B were comparable. 相似文献
7.
Antitumor properties of vindesine-monoclonal antibody conjugates 总被引:4,自引:0,他引:4
G. F. Rowland C. A. Axton R. W. Baldwin J. P. Brown J. R. F. Corvalan M. J. Embleton V. A. Gore I. Hellström K. E. Hellström E. Jacobs C. H. Marsden M. V. Pimm R. G. Simmonds W. Smith 《Cancer immunology, immunotherapy : CII》1985,19(1):1-7
Summary The anticancer alkaloid vindesine (VDS) was conjugated to four mouse monoclonal antibodies recognizing human tumor-associated antigens. The antibodies were 96.5 (antimelanoma, IgG2a); 791T/36 (antiosteogenic sarcoma, IgG2b); 11.285.14, and 14.95.55 (anticarcinoembryonic antigen, IgG1 and IgG2a respectively). Conjugates VDS-96.5 and VDS-791T/36 were tested in vitro and shown to be specifically cytotoxic for target cells expressing the appropriate antigen. The in vivo effects of the antibodies and conjugates were tested against human tumor xenografts in athymic or immunodeprived mice using multiple treatments. Conjugate VDS-96.5 retarded the initial growth of a melanoma xenograft, whereas free antibody was without effect. Similarly, VDS-791T/36 but not free antibody retarded the growth of osteogenic sarcoma 791T. The most marked antitumor effects observed were those obtained with VDS conjugates of the anti-CEA antibodies against a colorectal tumor xenograft. Antibody 14.95.55 suppressed tumor growth both alone and as a VDS conjugate, whereas 11.285.14 produced only a slight effect alone but an almost complete and lasting suppression of tumor growth as a VDS conjugate. Free VDS had little effect at nontoxic levels. Acute studies showed that VDS-11.285.14 conjugate was considerably less toxic than free VDS in Balb/c mice. 相似文献
8.
Biological characterization of human monoclonal antibodies to rabies virus. 总被引:9,自引:2,他引:7
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
B Dietzschold M Gore P Casali Y Ueki C E Rupprecht A L Notkins H Koprowski 《Journal of virology》1990,64(6):3087-3090
Rabies virus antigen-specific human monoclonal antibodies (MAbs) that recognized either viral glycoprotein, ribonucleoprotein, or matrix proteins were generated. Only glycoprotein-specific MAb neutralized a variety of rabies viruses and protected laboratory rodents against lethal rabies virus infection. The determinant recognized by this MAb does not appear to reside in previously defined antigenic sites of the viral glycoprotein. 相似文献
9.
Induction of rabies virus-specific T-helper cells by synthetic peptides that carry dominant T-helper cell epitopes of the viral ribonucleoprotein. 总被引:10,自引:4,他引:6
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
H C Ertl B Dietzschold M Gore L Otvos Jr J K Larson W H Wunner H Koprowski 《Journal of virology》1989,63(7):2885-2892
The T-helper cell response to the internal proteins of rabies virus was investigated. The rabies virus nucleoprotein was shown to be a major target antigen for T-helper cells that cross-react between rabies and rabies-related viruses. T-helper cells were assayed in vitro by testing virus-induced lymphocytes for lymphokine secretion in response to antigen. Immunodominant T-helper cell epitopes of the viral nucleoprotein were identified in vitro by using synthetic peptides delineated from the amino acid sequence of the nucleoprotein. The response to synthetic peptides were under Ir gene control. Antigenic peptides were tested in vivo for stimulation of rabies virus-specific T-helper cells. Inoculation of mice with peptides bearing immunodominant T-helper cell epitopes resulted in an accelerated and enhanced neutralizing antibody response upon booster immunization with inactivated rabies virus. 相似文献
10.
Data are reported on the net recovery O2 consumption (VO2) for nine male subjects (mean age 21.9 yr, VO2max 63.0 ml.kg-1.min-1, body fat 10.6%) used in a 3 (independent variables: intensities of 30, 50, and 70% VO2max) x 3 (independent variables: durations of 20, 50, and 80 min) repeated measures design (P less than or equal to 0.05). The 8-h mean excess postexercise O2 consumptions (EPOCs) for the 20-, 50-, and 80-min bouts, respectively, were 1.01, 1.43, and 1.04 liters at 30% VO2max (6.8 km/h); 3.14, 5.19, and 6.10 liters at 50% VO2max (9.5 km/h); and 5.68, 10.04, and 14.59 liters at 70% VO2max (13.4 km/h). The mean net total O2 costs (NTOC = net exercise VO2 + EPOC) for the 20-, 50-, and 80-min bouts, respectively, were 20.48, 53.20, and 84.23 liters at 30% VO2max; 38.95, 100.46, and 160.59 liters at 50% VO2max; and 58.30, 147.48, and 237.17 liters at 70% VO2max. The nine EPOCs ranged only from 1.0 to 8.9% of the NTOC (mean 4.8%) of the exercise. These data, therefore, indicate that in well-trained subjects the 8-h EPOC per se comprises a very small percentage of the NTOC of exercise. 相似文献