全文获取类型
收费全文 | 309篇 |
免费 | 51篇 |
专业分类
360篇 |
出版年
2022年 | 3篇 |
2021年 | 5篇 |
2020年 | 7篇 |
2019年 | 5篇 |
2017年 | 6篇 |
2016年 | 7篇 |
2015年 | 21篇 |
2014年 | 13篇 |
2013年 | 8篇 |
2012年 | 16篇 |
2011年 | 13篇 |
2010年 | 12篇 |
2009年 | 12篇 |
2008年 | 15篇 |
2007年 | 6篇 |
2006年 | 13篇 |
2005年 | 8篇 |
2004年 | 7篇 |
2003年 | 12篇 |
2002年 | 9篇 |
2001年 | 11篇 |
2000年 | 6篇 |
1999年 | 6篇 |
1998年 | 5篇 |
1993年 | 6篇 |
1992年 | 5篇 |
1991年 | 6篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 8篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1981年 | 5篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 7篇 |
1976年 | 4篇 |
1974年 | 3篇 |
1972年 | 2篇 |
1970年 | 5篇 |
1969年 | 8篇 |
1968年 | 5篇 |
1967年 | 2篇 |
1965年 | 4篇 |
1964年 | 5篇 |
1961年 | 3篇 |
1957年 | 2篇 |
排序方式: 共有360条查询结果,搜索用时 8 毫秒
81.
Jamie McIntosh Godwin Dennison Jeff M. P. Holly Caroline Jarrett Alexandra Frankow Emily J. Foulstone Zoe E. Winters Claire M. Perks 《The Journal of biological chemistry》2010,285(50):38788-38800
Progression of breast cancer is associated with remodeling of the extracellular matrix, often involving a switch from estrogen dependence to a dependence on EGF receptor (EGFR)/HER-2 and is accompanied by increased expression of the main binding protein for insulin-like growth factors (IGFBP-3). We have examined the effects of IGFBP-3 on EGF responses of breast epithelial cells in the context of changes in the extracellular matrix. On plastic and laminin with MCF-10A normal breast epithelial cells, EGF and IGFBP-3 each increased cell growth and together produced a synergistic response, whereas with T47D breast cancer cells IGFBP-3 alone had no effect, but the ability of EGF to increase cell proliferation was markedly inhibited in the presence of IGFBP-3. In contrast on fibronectin with MCF-10A cells, IGFBP-3 alone inhibited cell growth and blocked EGF-induced proliferation. With the cancer cells, IGFBP-3 alone had no effect but enhanced the EGF-induced increase in cell growth. The insulin-like growth factor-independent effects of IGFBP-3 alone on cell proliferation were completely abrogated in the presence of an EGFR, tyrosine kinase inhibitor, Iressa. Although IGFBP-3 did not affect EGFR phosphorylation [Tyr1068], it was found to modulate receptor internalization and was associated with activation of Rho and subsequent changes in MAPK phosphorylation. The levels of fibronectin and IGFBP-3 within breast tumors may determine their dependence on EGFR and their response to therapies targeting this receptor. 相似文献
82.
Plague is a flea-borne zoonosis caused by the bacterium Yersinia pestis. Y. pestis mutants lacking the yersiniabactin (Ybt) siderophore-based iron transport system are avirulent when inoculated intradermally but fully virulent when inoculated intravenously in mice. Presumably, Ybt is required to provide sufficient iron at the peripheral injection site, suggesting that Ybt would be an essential virulence factor for flea-borne plague. Here, using a flea-to-mouse transmission model, we show that a Y. pestis strain lacking the Ybt system causes fatal plague at low incidence when transmitted by fleas. Bacteriology and histology analyses revealed that a Ybt-negative strain caused only primary septicemic plague and atypical bubonic plague instead of the typical bubonic form of disease. The results provide new evidence that primary septicemic plague is a distinct clinical entity and suggest that unusual forms of plague may be caused by atypical Y. pestis strains. 相似文献
83.
84.
Cytochrome P450 2C9 (CYP2C9)-mediated flurbiprofen 4'-hydroxylation is activated by the presence of dapsone resulting in reduction of the K(m) for flurbiprofen hydroxylation and an increase in V(m). Previous spectral binding studies have demonstrated that the binding of flurbiprofen with CYP2C9 is increased (decrease in K(S)) by the presence of dapsone. We hypothesized that the two compounds are simultaneously in the active site with the presence of dapsone causing flurbiprofen to be oriented more closely to the heme. T(1) relaxation rates determined by NMR were used to estimate the distances of protons on these compounds from the paramagnetic heme-iron center. Samples contained 0.014 microM CYP2C9 and 145 microM flurbiprofen in the presence and absence of 100 microM dapsone. Estimated distances of various flurbiprofen protons from the heme ranged from 4.2 to 4.5 A in the absence of dapsone and from 3.2 to 3.8 A in the presence of dapsone. The 4' proton of flurbiprofen, the site of metabolism, showed one of the greatest differences in distance from the heme in the presence of dapsone, 3.50 A, as compared to the absence of dapsone, 4.41 A. Dapsone protons were less affected, being 4.40 A from the heme in the absence of flurbiprofen and 4.00-4.01 A from the heme in the presence of flurbiprofen. Molecular modeling studies were also performed to corroborate the relative orientations of flurbiprofen and dapsone in the active site of CYP2C9. Shift of the 4' proton of flurbiprofen closer to the heme iron of CYP2C9 in the presence of dapsone may play a role in activation. 相似文献
85.
This report provides a detailed analysis of developmental changes in cytoplasmic free calcium (Ca(2+)) buffering and excitation-contraction coupling in embryonic chick ventricular myocytes. The peak magnitude of field-stimulated Ca(2+) transients declined by 41% between embryonic day (ED) 5 and 15, with most of the decline occurring between ED5 and 11. This was due primarily to a decrease in Ca(2+) currents. Sarcoplasmic reticulum (SR) Ca(2+) content increased 14-fold from ED5 to 15. Ca(2+) transients in voltage-clamped myocytes after blockade of SR function permitted computation of the fast Ca buffer power of the cytosol as expressed as generalized values of B(max) and K(D). B(max) rose with development whereas K(D) did not change significantly. The computed SR Ca(2+) contribution to the Ca(2+) transient and gain factor for Ca(2+)-induced Ca(2+) release increased markedly between ED5 and 11 and slightly thereafter. These results paralleled the maturation of SR and peripheral couplings reported by others and demonstrated a strong relationship between structure and function in development of excitation-contraction coupling. Modeling of buffer power from estimates of the major cytosolic Ca binding moieties yielded a B(max) and K(D) in reasonable agreement with experiment. From ED5 to 15, troponin C was the major Ca(2+) binding moiety, followed by SR and calmodulin. 相似文献
86.
IKKalpha regulates mitogenic signaling through transcriptional induction of cyclin D1 via Tcf 总被引:7,自引:0,他引:7 下载免费PDF全文
87.
A monoclonal antibody which blocks infection with feline immunodeficiency virus identifies a possible non-CD4 receptor. 总被引:10,自引:5,他引:5 下载免费PDF全文
Monoclonal antibody vpg15 detects a 24-kDa cell surface protein on feline cells permissive for infection with feline immunodeficiency virus (FIV). The antibody blocks infection of FIV-susceptible cells, and expression of the vpg15 marker is decreased in FIV-infected cells in vitro. These results suggest that the antibody may recognize an FIV receptor distinct from CD4. 相似文献
88.
Sarah C. Tryon Iris M. Sakamoto Kris F. Kaigler Gabriella Gee Jarrett Turner Katherine Bartley Jim R. Fadel Marlene A. Wilson 《Genes, Brain & Behavior》2023,22(1):e12837
The cholinergic system is a critical regulator of Pavlovian fear learning and extinction. As such, we have begun investigating the cholinergic system's involvement in individual differences in cued fear extinction using a transgenic ChAT::Cre rat model. The current study extends behavioral phenotyping of a transgenic ChAT::Cre rat line by examining both freezing behavior and ultrasonic vocalizations (USVs) during a Pavlovian cued fear learning and extinction paradigm. Freezing, 22 kHz USVs, and 50 kHz USVs were compared between male and female transgenic ChAT::Cre+ rats and their wildtype (Cre-) littermates during fear learning, contextual and cue-conditioned fear recall, cued fear extinction, and generalization to a novel tone. During contextual and cued fear recall ChAT::Cre+ rats froze slightly more than their Cre- littermates, and displayed significant sex differences in contextual and cue-conditioned freezing, 22 kHz USVs, and 50 kHz USVs. Females showed more freezing than males in fear recall trials, but fewer 22 kHz distress calls during fear learning and recall. Females also produced more 50 kHz USVs during exposure to the testing chambers prior to tone (or shock) presentation compared with males, but this effect was blunted in ChAT::Cre+ females. Corroborating previous studies, ChAT::Cre+ transgenic rats overexpressed vesicular acetylcholine transporter immunolabeling in basal forebrain, striatum, basolateral amygdala, and hippocampus, but had similar levels of acetylcholinesterase and numbers of ChAT+ neurons as Cre- rats. This study suggests that variance in behavior between ChAT::Cre+ and wildtype rats is sex dependent and advances theories that distinct neural circuits and processes regulate sexually divergent fear responses. 相似文献
89.
Twenty-eight men were given morning and afternoon oral glucose tolerance tests in 1969 and again in 1975. According to British Diabetic Association criteria all 28 had normal morning values in 1969 but seven had "afternoon diabetes". Four men had diabetic values in the morning in 1975 but only two of these had had afternoon diabetes in 1969. Better prediction of subsequent diabetes was obtained by calculating the area under the morning glucose tolerance curve in 1969. All four men who progressed to diabetes had areas exceeding 1000 units, which distinguished them absolutely from the other 24. They also tended to be more obese, but this was less predictive of subsequent diabetes. 相似文献
90.
Fourteen patients with longstanding lipodermatosclerosis of their lower legs, secondary to venous disease in 11, were treated for three months with stanozolol, a drug that enhances fibrinolytic activity. No other treatment was given and no change made in existing treatment. All the patients improved. Two were cured in three months, three were able to stop treatment in the next three to 11 months, and the other nine continued to improve. Fibrinolytic enhancement, with stanozolol, seems to be a worthwhile addition to the treatment of venous liposclerosis and deserves further study. 相似文献