全文获取类型
收费全文 | 622篇 |
免费 | 49篇 |
国内免费 | 3篇 |
出版年
2024年 | 2篇 |
2022年 | 5篇 |
2021年 | 6篇 |
2020年 | 3篇 |
2018年 | 7篇 |
2017年 | 8篇 |
2016年 | 10篇 |
2015年 | 22篇 |
2014年 | 23篇 |
2013年 | 33篇 |
2012年 | 43篇 |
2011年 | 30篇 |
2010年 | 27篇 |
2009年 | 26篇 |
2008年 | 34篇 |
2007年 | 41篇 |
2006年 | 34篇 |
2005年 | 29篇 |
2004年 | 31篇 |
2003年 | 25篇 |
2002年 | 16篇 |
2001年 | 26篇 |
2000年 | 17篇 |
1999年 | 26篇 |
1998年 | 17篇 |
1997年 | 8篇 |
1996年 | 9篇 |
1995年 | 13篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 11篇 |
1991年 | 10篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 10篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1971年 | 2篇 |
1966年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有674条查询结果,搜索用时 15 毫秒
41.
42.
O'Reilly LA Divisekera U Newton K Scalzo K Kataoka T Puthalakath H Ito M Huang DC Strasser A 《Cell death and differentiation》2004,11(7):724-736
The adaptor protein FADD/MORT1 is essential for apoptosis induced by 'death receptors', such as Fas (APO-1/CD95), mediating aggregation and autocatalytic activation of caspase-8. Perhaps surprisingly, FADD and caspase-8 are also critical for mitogen-induced proliferation of T lymphocytes. We generated novel monoclonal antibodies specific for mouse FADD and caspase-8 to investigate whether cellular responses, apoptosis or proliferation, might be explained by differences in post-translational modification and subcellular localisation of these proteins. During both apoptosis signalling and mitogenic activation, FADD and caspase-8 aggregated in multiprotein complexes and formed caps at the plasma membrane but they did not colocalise with lipid rafts. Interestingly, mitogenic stimulation, but not Fas ligation, induced a unique post-translational modification of FADD. These different modifications may determine whether FADD and caspase-8 induce cell death or proliferation. 相似文献
43.
Goltsev V Zaharieva I Lambrev P Yordanov I Strasser R 《Journal of theoretical biology》2003,225(2):171-183
An attempt is made to reveal the relation between the induction curves of delayed fluorescence (DF) registered at 0.35-5.5 ms and the prompt chlorophyll fluorescence (PF). A simple formulation was proposed to link the ratio of the transient values of delayed and variable fluorescence with the redox state of the primary electron acceptor of Photosystem II--QA, and the thylakoid membrane energization. The term luminescence potential (UL) was introduced, defined as the sum of the redox potential of QA and the transmembrane proton gradient. It was shown that UL is proportional to the ratio of DF to the variable part of PF. The theoretical model was verified and demonstrated by analysing induction courses of PF and millisecond DF, simultaneously registered from leaves of barley--wild-type and the chlorophyll b-less mutant chlorina f2. A definitive correlation between PF and DF was established. If the luminescence changes are strictly due to UL, the courses of DF and PF are reciprocal and the millisecond DF curve resembles the first derivative of the PFt function. 相似文献
44.
Estrogen and its catechol metabolites from both the circulation and synthesized within the breast are important in the pathogenesis of breast cancer. Blocking estrogen's effects on the breast with selective estrogen receptor modulators (SERMS) is an ongoing strategy. Thus, tamoxifen and raloxifene reduce risk as monotherapy. Aromatase (estrogen synthetase) inhibitors are a logical alternative to SERMS. To date, SERMS have demonstrated reduction only in estrogen–progesterone receptor positive cancers without reduction in receptor negative tumors. By inhibiting the parent estrogens and their catechol metabolites, true prevention of cancer initiation might occur and reduction not only in the receptor positive but also negative tumors might result. Ongoing adjuvant breast cancer trials are exploring aromatase inhibitors as alternatives to tamoxifen, or in sequence or in combination with tamoxifen. Relative efficacies including reduction in contralateral breast cancer, toxicities and end-organ effects and impact on quality of life, are being explored. Data from these trials will help to guide future chemoprevention strategies. Proof of principal trials in ‘high risk’ cohorts such as premalignant breast lesions, dense screening mammograms, high plasma estradiol levels or increased bone density are already ongoing. Issues such as dose, schedule, therapeutic index and mono versus combination therapy are important to define. 相似文献
45.
Induction of BIM, a proapoptotic BH3-only BCL-2 family member, is critical for neuronal apoptosis 总被引:41,自引:0,他引:41
Sympathetic neuronal death induced by nerve growth factor (NGF) deprivation requires the macromolecular synthesis-dependent translocation of BAX from the cytosol to mitochondria and its subsequent integration into the mitochondrial outer membrane, followed by BAX-mediated cytochrome c (cyt c) release. The gene products triggering this process remain unknown. Here, we report that BIM, a member of the BH3-only proapoptotic subfamily of the BCL-2 protein family, is one such molecule. NGF withdrawal induced expression of BIM(EL), an integral mitochondrial membrane protein that functions upstream of (or in parallel with) the BAX/BCL-2 and caspase checkpoints. Bim deletion conferred protection against developmental and induced neuronal apoptosis in both central and peripheral populations, but only transiently, suggesting that BIM--and perhaps other BH3-only proteins--serve partially redundant functions upstream of BAX-mediated cyt c release. 相似文献
46.
Role of the spindle pole body of yeast in mediating assembly of the prospore membrane during meiosis 总被引:6,自引:0,他引:6
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Spindle pole bodies (SPBs) are the centrosome equivalents in yeast, required for microtubule organization. In yeast, the SPB further serves as the attachment sites of the prospore membrane during meiosis. Here we report the identification of two new meiosis-specific components of the SPB, Mpc54p and Mpc70p, and the first protein specific for the prospore membrane, Don1p. Mpc54p and Mpc70p are not present in mitotic SPBs, and during meiosis II they are components of a meiosis-specific structural alteration of the outer plaque of the SPB. Both proteins are dispensable for the meiotic divisions but are essentially required for the formation of the prospore membrane. In the mpc54 and mpc70 mutants, the Don1p-containing precursors of the prospore membrane can still be found in the cytoplasm and associated with the SPB. Unexpectedly, however, the assembly of the precursors to a continuous membrane system is affected. Thus, the meiotic SPB is directly involved in the formation of a specialized membrane system, the membrane of the prospore. 相似文献
47.
Villunger A Huang DC Holler N Tschopp J Strasser A 《Journal of immunology (Baltimore, Md. : 1950)》2000,165(3):1337-1343
Jun kinase signaling can be elicited by death receptor activation, but the mechanism and significance of this event are still unclear. It has been reported that cross-linking Abs to Fas trigger c-Jun N-terminal kinase (JNK) signaling via caspase-mediated activation of MEKK1 (JNK kinase kinase), elevation of ceramide levels or by recruitment of death domain associated protein (DAXX) to Fas. The effect of physiological ligand for Fas on JNK signaling was never investigated, although evidence is accumulating that Fas ligand is able to induce cellular responses distinct from those evoked by Ab-mediated cross-linking of Fas. Therefore, we investigated the effect of Fas ligand on JNK signaling. Like its ability to induce cell death, Fas ligand reliably activated JNK only upon extensive aggregation of the receptor. Although this was partially dependent on caspase activation, DAXX was not required. DAXX and other death receptor-associated proteins, which have been reported to bind directly or indirectly to Fas, such as receptor interacting protein (RIP) and RIP-associated ICH-1/CED-3-homologous protein with a death domain (RAIDD), were shown to be dispensable for Fas ligand-induced apoptosis. 相似文献
48.
49.
Rod and cone photoreceptors project from the outer retinal surface into a
carbohydrate-rich interphotoreceptor matrix (IPM). Unique IPM
glycoconjugates are distributed around rods and cones. Wheat germ
agglutinin (WGA) strongly decorates the rod matrix domains and weakly
decorates the cone matrix domains. This study characterizes the major
WGA-binding glycoprotein in the human IPM, which we refer to as SPACR
(sialoprotein associated with cones and rods). SPACR, which has a molecular
weight of 147 kDa, was isolated and purified from the IPM by lectin
affinity chromatography. A polyclonal antibody to SPACR was prepared that
colocalizes in tissue preparations with WGA-binding domains in the IPM.
Sequential digestion of SPACR with N- and O- glycosidases results in a
systematic increase in electrophorectic mobility, indicating the presence
of both N- and O-linked glycoconjugates. Complete deglycosylation results
in a reduction in the relative molecular mass of SPACR by about 30%.
Analysis of lectin binding allowed us to identify some of the structural
characteristics of SPACR glycoconjugates. Treatment with neuraminidase
exposes Galbeta1- 3GalNAc disaccharide as indicated by positive peanut
agglutinin (PNA) staining, accompanied by the loss of WGA staining. Maackia
amurensis agglutinins (MAA-1 and MAA-2), specific for sialic acid in
alpha2-3 linkage to Gal, bind SPACR, while Sambucus nigra agglutinin (SNA),
specific for alpha2-6 linked sialic acid, does not, indicating that the
dominant glycoconjugate determinant on SPACR is the O-linked carbohydrate,
NeuAcalpha2-3Galbeta1-3GalNAc. The abundance of sialic acid in SPACR
suggests that this glycoprotein may contribute substantially to the
polyanionic nature of the IPM. The carbohydrate chains present on SPACR
could also provide sites for extensive crosslinking and participate in the
formation of the ordered IPM lattice that surrounds the elongate
photoreceptors projecting from the outer retinal surface.
相似文献
50.
Exoprotease activity of Leuconostoc oenos in stress conditions 总被引:1,自引:1,他引:0
Rollán Farías A.M. Strasser de Saad & M.C. Manca de Nadra 《Journal of applied microbiology》1998,85(2):219-223
Exoprotease activity during 48 h of total energy and nutrient starvation was examined in Leuconostoc oenos X2 L isolated from wine. Starved cells after 2 h of incubation at 30 °C in citrate buffer, 0.05 mmol 1−1 pH 5, showed greater extracellular proteolytic activity than at the onset of starvation. In the presence of 60 mg l−1 SO2 and 8% or 12% ethanol, the proteolytic activity was higher ; 10 mmol l−1 Ca2+ and Mg2+ produced an increase in protease activity during starvation. Glucose and 2-deoxyglucose (2-DOG) were found to repress synthesis by 80% and 100%, respectively. Cyclic adenosine 3'-5'-phosphate increased the exoprotease activity and reverted the repression by glucose and 2-DOG. De novo synthesis of proteins was required for the exoprotease activity by cells submitted to stress conditions. The absence of protease activity in the supernatant fluids from chloramphenicol-treated cells indicated that the activity is a result of deliberate release and not of passive cell lysis. 相似文献