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41.
Reemergence of carcinomas following chemotherapy and/or radiotherapy is not well understood, but a recent study in BMC Cancer suggests that resistance to apoptosis resulting from altered cell cycle regulation is crucial. 相似文献
42.
Stephen L. Abrams Linda S. Steelman John G. Shelton William Chappell J?rg B?secke Franca Stivala Marco Donia Ferdinando Nicoletti Massimo Libra Alberto M. Martelli James A. McCubrey 《Cell cycle (Georgetown, Tex.)》2010,9(9):1839-1846
The effects of inhibition of the Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways and chemotherapeutic drugs on cell cycle progression and drug sensitivity were examined in cytokine-dependent FL5.12 hematopoietic cells. We examined their effects, as these cells resemble normal hematopoietic precursor cells as they do not exhibit “oncogene-addicted” growth, while they do display “cytokine-addicted” proliferation as cytokine removal resulted in apoptosis in greater than 80% of the cells within 48 h. When cytokine-dependent FL5.12 cells were cultured in the presence of IL-3, which stimulated multiple proliferation and anti-apoptotic cascades, MEK, PI3K and mTOR inhibitors transiently suppressed but did not totally inhibit cell cycle progression or induce apoptosis while chemotherapeutic drugs such as doxorubicin and paclitaxel were more effective in inducing cell cycle arrest and apoptosis. Doxorubicin induced a G1 block, while paclitaxel triggered a G2/M block. Doxorubicin was more effective in inducing cell death than paclitaxel. Furthermore the effects of doxorubicin could be enhanced by addition of MEK, PI3K or mTOR inhibitors. Cytokine-dependent cells which proliferate in vitro and are not “oncogene-addicted” may represent a pre-malignant stage, more refractory to treatment with targeted therapy. However, these cells are sensitive to chemotherapeutic drugs. It is important to develop methods to inhibit the growth of such cytokine-dependent cells as they may resemble the leukemia stem cell and other cancer initiating cells. These results demonstrate the enhanced effectiveness of targeting early hematopoietic progenitor cells with combinations of chemotherapeutic drugs and signal transduction inhibitors. 相似文献
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Russell GA Chappell MA 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2007,177(1):75-87
Basal metabolic rate (BMR) is probably the most studied aspect of energy metabolism in vertebrate endotherms. Numerous papers
have explored its mass allometry, phylogenetic and ecological relationships, and ontogeny. Implicit in many of these studies
(and explicit in some) is the view that BMR responds to selection, which requires repeatability and heritability. However,
BMR is highly plastic in response to numerous behavioral and environmental factors and there are surprisingly few data on
its repeatability. Moreover, the mechanistic underpinnings of variation in BMR are unclear, despite considerable research.
We studied BMR repeatability in deer mice (Peromyscus maniculatus) across intervals of 30–60 days, and also examined the influence of birth altitude (3,800 m versus 340 m) and temperature
acclimation (to ∼5 or ∼20°C) on BMR, and the relationship between BMR and organ size. Neither acclimation temperature nor
natal altitude alone influenced BMR, but the combination of birth at high altitude and cold acclimation significantly increased
BMR. Few visceral organ masses were correlated to BMR and most were inconsistent across natal altitudes and acclimation temperatures,
indicating that no single organ ‘controls’ variation in BMR. In several treatment groups, the mass of the ‘running motor’
(combined musculoskeletal mass) was negatively correlated to BMR and the summed mass of visceral organs was positively correlated
to BMR. We found no repeatability of BMR in any treatment group. That finding—in sharp contrast to high repeatability of BMR
in several other small endotherms—suggests little potential for direct selection to drive BMR evolution in deer mice. 相似文献
45.
Yamaleyeva LM Pendergrass KD Pirro NT Gallagher PE Groban L Chappell MC 《American journal of physiology. Heart and circulatory physiology》2007,293(4):H2064-H2071
Studies in experimental animals and younger women suggest a protective role for estrogen; however, clinical trials may not substantiate this effect in older females. Therefore, the present study assessed the outcome of ovariectomy in older mRen2. Lewis rats subjected to a high-salt diet for 4 wk. Intact or ovariectomized (OVX, 15 wk of age) mRen2. Lewis rats were aged to 60 wk and then placed on a high-salt (HS, 8% sodium chloride) diet for 4 wk. Systolic blood pressures were similar between groups [OVX 169 +/- 6 vs. Intact 182 +/- 7 mmHg; P = 0.22] after the 4-wk diet; however, proteinuria [OVX 0.8 +/- 0.2 vs. Intact 11.5 +/- 2.6 mg/mg creatinine; P < 0.002, n = 6], renal interstitial fibrosis, glomerular sclerosis, and tubular casts were lower in OVX vs. Intact rats. Kidney injury molecule-1 mRNA, a marker of tubular damage, was 53% lower in the OVX HS group. Independent from blood pressure, OVX HS rats exhibited significantly lower cardiac (24%) and renal (32%) hypertrophy as well as lower C-reactive protein (28%). Circulating insulin-like growth factor-I (IGF-I) levels were not different between the Intact and OVX groups; however, renal cortical IGF-I mRNA and protein were attenuated in OVX rats [P < 0.05, n = 6]. We conclude that ovariectomy in the older female mRen2. Lewis rat conveys protection against salt-dependent increase in renal injury. 相似文献
46.
Rachaneeporn Tiyawisutsri Matthew TG Holden Sarinna Tumapa Sirirat Rengpipat Simon R Clarke Simon J Foster William C Nierman Nicholas PJ Day Sharon J Peacock 《BMC microbiology》2007,7(1):19
Background
The bacterial biothreat agents Burkholderia mallei and Burkholderia pseudomallei are the cause of glanders and melioidosis, respectively. Genomic and epidemiological studies have shown that B. mallei is a recently emerged, host restricted clone of B. pseudomallei. 相似文献47.
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Demery ZP Chappell J Martin GR 《Proceedings. Biological sciences / The Royal Society》2011,278(1725):3687-3693
Parrots are exceptional among birds for their high levels of exploratory behaviour and manipulatory abilities. It has been argued that foraging method is the prime determinant of a bird's visual field configuration. However, here we argue that the topography of visual fields in parrots is related to their playful dexterity, unique anatomy and particularly the tactile information that is gained through their bill tip organ during object manipulation. We measured the visual fields of Senegal parrots Poicephalus senegalus using the ophthalmoscopic reflex technique and also report some preliminary observations on the bill tip organ in this species. We found that the visual fields of Senegal parrots are unlike those described hitherto in any other bird species, with both a relatively broad frontal binocular field and a near comprehensive field of view around the head. The behavioural implications are discussed and we consider how extractive foraging and object exploration, mediated in part by tactile cues from the bill, has led to the absence of visual coverage of the region below the bill in favour of more comprehensive visual coverage above the head. 相似文献
50.