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61.
BCL-xL: time-dependent dissociation between modulation of apoptosis and invasiveness in human malignant glioma cells 总被引:2,自引:0,他引:2
Weiler M Bähr O Hohlweg U Naumann U Rieger J Huang H Tabatabai G Krell HW Ohgaki H Weller M Wick W 《Cell death and differentiation》2006,13(7):1156-1169
Conditionally BCL-xL-overexpressing LNT-229 Tet-On glioma cell clones were generated to investigate whether the 'antiapoptosis phenotype' and the 'motility phenotype' mediated by BCL-2 family proteins in glioma cells could be separated. BCL-xL induction led to an immediate and concentration-dependent protection of LNT-229 cells from apoptosis. BCL-xL induction for up to 3 days did not result in altered invasiveness. In contrast, long-term BCL-xL induction for 21 days resulted in increased transforming growth factor-beta2 expression, and in metalloproteinase-2 and -14 dependent, but integrin independent, increased invasiveness. Withdrawal of doxycycline (Dox) abolished the protection from apoptosis whereas the 'invasion phenotype' remained stable. Dox stimulation of BCL-xL-inducible LNT-229 cells conferred infiltrative growth to BCL-xL-positive glioma cells in vivo and reduced the survival of tumor-bearing mice. These data allow to dissect a direct antiapoptotic action of BCL-xL from an indirect effect, presumably mediated by altered gene expression, which modifies tumor cell invasiveness in vitro and in vivo. 相似文献
62.
Recent progress in understanding the biosynthesis of the auxin, indole-3-acetic acid (IAA) in Arabidopsis thaliana is reviewed. The current situation is characterized by considerable progress in identifying, at the molecular level and in functional terms, individual reactions of several possible pathways. It is still too early to piece together a complete picture, but it becomes obvious that A. thaliana has multiple pathways of IAA biosynthesis, not all of which may operate at the same time and some only in particular physiological situations. There is growing evidence for the presence of an indoleacetamide pathway to IAA in A. thaliana, hitherto known only from certain plant-associated bacteria, among them the phytopathogen Agrobacterium tumefaciens. 相似文献
63.
Polymorphisms in several host genes in HIV-infected individuals facilitate slow progression to AIDS. We have identified several SIV-infected Indian rhesus macaques that naturally control viral replication. We investigated whether spontaneous control of SIV in any of these animals could be explained by mutations in host genes. Such variables could confound studies of associations between MHC class I alleles and control of viral replication. We searched for polymorphisms in CCR5, CXCR6, GPR15, RANTES, IL-10, APOBEC3G, TNF-α, and TSG101 and looked for associations with decreased viral replication. We did not detect any correlations between plasma viral concentration and polymorphisms in host genes examined in this study. In addition, we did not find the polymorphisms present in humans in any of our macaques.Nucleotide sequence data reported are available in the GenBank database under accession numbers DQ890030–DQ890063, DQ887987–DQ888038, DQ902356–DQ902543, and DQ913647–DQ913733. 相似文献
64.
A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome c during apoptosis. 总被引:15,自引:0,他引:15
Luca Scorrano Mona Ashiya Karolyn Buttle Solly Weiler Scott A Oakes Carmen A Mannella Stanley J Korsmeyer 《Developmental cell》2002,2(1):55-67
The mechanism during apoptosis by which cytochrome c is rapidly and completely released in the absence of mitochondrial swelling is uncertain. Here, we show that two distinct pathways are involved. One mediates release of cytochrome c across the outer mitochondrial membrane, and another, characterized in this study, is responsible for the redistribution of cytochrome c stored in intramitochondrial cristae. We have found that the "BH3-only" molecule tBID induces a striking remodeling of mitochondrial structure with mobilization of the cytochrome c stores (approximately 85%) in cristae. This reorganization does not require tBID's BH3 domain and is independent of BAK, but is inhibited by CsA. During this process, individual cristae become fused and the junctions between the cristae and the intermembrane space are opened. 相似文献
65.
Joseph HA Vissers Francesco Nicassio Maarten van Lohuizen Pier Paolo Di Fiore Elisabetta Citterio 《Cell division》2008,3(1):1-14
Increasing knowledge on the cell cycle deregulations in cancers has promoted the introduction of phytochemicals, which can either modulate signaling pathways leading to cell cycle regulation or directly alter cell cycle regulatory molecules, in cancer therapy. Most human malignancies are driven by chromosomal translocations or other genetic alterations that directly affect the function of critical cell cycle proteins such as cyclins as well as tumor suppressors, e.g., p53. In this respect, cell cycle regulation and its modulation by curcumin are gaining widespread attention in recent years. Extensive research has addressed the chemotherapeutic potential of curcumin (diferuloylmethane), a relatively non-toxic plant derived polyphenol. The mechanisms implicated are diverse and appear to involve a combination of cell signaling pathways at multiple levels. In the present review we discuss how alterations in the cell cycle control contribute to the malignant transformation and provide an overview of how curcumin targets cell cycle regulatory molecules to assert anti-proliferative and/or apoptotic effects in cancer cells. The purpose of the current article is to present an appraisal of the current level of knowledge regarding the potential of curcumin as an agent for the chemoprevention of cancer via an understanding of its mechanism of action at the level of cell cycle regulation. Taken together, this review seeks to summarize the unique properties of curcumin that may be exploited for successful clinical cancer prevention. 相似文献
66.
Weiler HA Fitzpatrick S Fitzpatrick-Wong SC 《The Journal of nutritional biochemistry》2008,19(11):762-769
Previously, a mixture of conjugated linoleic acid (CLA) isoforms reduced parathyroid hormone (PTH) in male rats over 8 weeks. The objective herein was to determine which isoform caused the reduction in PTH; whether the effect was sex specific; and whether CLA-induced reductions in PTH were sustained. Male and female weanling rats (n=48) were randomized to a control diet or one made with 0.5% of the diet as cis-9, trans-11 (c9,t11) CLA, 0.5% of the diet as trans-10, cis-12 (t10,c12) CLA or these CLA in a mixture. Measurements made after 4, 8 and 16 weeks were body weight, bioactive PTH, ionized Ca, whole-body and regional bone mineral density (BMD) using dual-energy X-ray absorptiometry. With the use of a factorial design, a sexxc9,t11 CLA interaction was observed that reduced PTH (139.5+/-63.9 vs. 95.8+/-42.4 pg/ml, P=.02) in male rats only. No other effects of c9,t11 CLA were observed. Regarding t10,c12 CLA, no interaction effects were observed, but a main effect was observed to reduce lumbar spine BMD (0.265+/-0.044 vs. 0.255+/-0.044 g/cm(2), P<.01) along with reduced retention of Ca and P at Week 4. No other dietary effects were observed. In summary, the c9,t11 CLA isoform is responsible for reduced PTH and this effect is sex specific; this was true whether fed as a pure isomer or mixed with an equal amount of t10,c12 CLA. Whether such reductions in PTH might be observed in females lacking sex hormones such as ovariectomized rats and also in humans is required to expand health implications of dietary CLA. 相似文献
67.
68.
Hepatocarcinogenesis in rats produced by prolonged feeding of thioacetamide appears as a progressive phenomenon in which morphological changes are associated with important biochemical modifications. It seems most likely that changes in the permeability of cell membrane induced by the carcinogen are responsible for increased intracellular accumulation of Ca2+, and for the ensuring of cell injury produced by Ca2+ overloading of the mitochondria. This calcification of the mitochondria may play a role in the neoplastic transformation of the cell, especially as far as it concerns metabolic behavior and the genetic specification of the permeability characteristics of the transformed cell membrane. The increased synthesis of acid glycosaminoglycans suggests their involvement in calcium-mediated control of tumor development and growth. 相似文献
69.
70.
P J O'Brien H Shen J Weiler C D Ianuzzo C Wittnich G W Moe P W Armstrong 《Canadian journal of physiology and pharmacology》1991,69(2):262-268
The development of muscle fatigue due to exhaustive exercise is associated with impaired sarcoplasmic reticulum (SR) Ca-transport activity. This study tested the hypothesis that SR failure is a consistent feature of cardiac and skeletal muscle fatigue owing to relative functional overload regardless of the method of induction: excessive stimulation, diminished performance capacity, or excessive excitation-contraction coupling. The Ca-transport activity was determined using three unique models of muscle fatigue: chronic and rapid ventricular pacing in dogs; metabolic inhibition caused by global cardiac ischemia in swine; and the hypermetabolic syndrome of porcine malignant hyperthermia (MH). Both pacing- and ischemia-induced fatigue resulted in reduction of SR Ca-transport ATPase activity: from 275 +/- 58 to 159 +/- 57 nmol.min-1.mg-1 (mU/mg) and from 577 +/- 82 to 177 +/- 133 mU/mg, respectively. Both pacing-induced fatigue and halothane-induced MH resulted in reduction of Ca-sequestration activity of muscle homogenates from 5.95 +/- 2.4 to 3.11 +/- 0.67 nM/s at 300 nM Ca and 38.7 +/- 10.5 to 16.3 +/- 8.0 nM/s at 1500 nM Ca, respectively (all p less than 0.01). The isolated SR Ca-ATPase activity correlated with Ca-sequestration activity of myocardial homogenates (r = 0.76; p less than 0.005). Different models were used to study the relationship of Ca-transport activity with relaxation function, degree of acidosis, and ionized Ca concentration.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献