全文获取类型
收费全文 | 1019篇 |
免费 | 72篇 |
专业分类
1091篇 |
出版年
2023年 | 8篇 |
2022年 | 16篇 |
2021年 | 30篇 |
2020年 | 18篇 |
2019年 | 8篇 |
2018年 | 25篇 |
2017年 | 13篇 |
2016年 | 27篇 |
2015年 | 41篇 |
2014年 | 45篇 |
2013年 | 62篇 |
2012年 | 86篇 |
2011年 | 74篇 |
2010年 | 46篇 |
2009年 | 34篇 |
2008年 | 60篇 |
2007年 | 40篇 |
2006年 | 36篇 |
2005年 | 40篇 |
2004年 | 29篇 |
2003年 | 33篇 |
2002年 | 18篇 |
2001年 | 32篇 |
2000年 | 16篇 |
1999年 | 16篇 |
1998年 | 5篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 7篇 |
1993年 | 5篇 |
1992年 | 13篇 |
1991年 | 12篇 |
1990年 | 17篇 |
1989年 | 9篇 |
1988年 | 14篇 |
1987年 | 12篇 |
1986年 | 9篇 |
1985年 | 12篇 |
1984年 | 6篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1980年 | 9篇 |
1979年 | 13篇 |
1978年 | 4篇 |
1973年 | 13篇 |
1972年 | 11篇 |
1971年 | 9篇 |
1970年 | 6篇 |
1966年 | 3篇 |
排序方式: 共有1091条查询结果,搜索用时 0 毫秒
191.
Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP-on-chip 总被引:1,自引:1,他引:0
Shilpi Arora Yipeng Wang Zhenyu Jia Saynur Vardar-Sengul Ayla Munawar Kutbuddin S Doctor Michael Birrer Michael McClelland Eileen Adamson Dan Mercola 《Genome biology》2008,9(11):R166
Background
UV irradiation activates the epidermal growth factor receptor, induces Egr1 expression and promotes apoptosis in a variety of cell types. We examined the hypothesis that Egr1 regulates genes that mediate this process by use of a chip-on-chip protocol in human tumorigenic prostate M12 cells. 相似文献192.
193.
194.
Taruna Arora Rupa Padaki Ling Liu Agnes E. Hamburger Aaron R. Ellison Seth R. Stevens James S. Louie Tadahiko Kohno 《Cytokine》2009,45(2):124-131
There are currently two Food and Drug Administration-approved classes of biologic agents that target tumor necrosis factor-α (TNF-α): anti-TNF monoclonal antibodies (mAbs) (adalimumab and infliximab), and soluble TNF receptors (etanercept). This study examined the ability of the TNF antagonists to: (1) bind various polymorphic variants of cell surface-expressed Fc receptors (FcγRs) and the complement component C1q, and (2) mediate Ab-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) killing of cells expressing membrane-bound TNF (mTNF) in vitro. Both mAbs and the soluble TNF receptor demonstrated low-level binding to the activating receptors FcγRI, FcγRIIa, and FcγRIIIa, and the inhibitory receptor FcγRIIb, in the absence of exogenous TNF. However, upon addition of TNF, the mAbs, but not etanercept, showed significantly increased binding, in particular to the FcγRII and FcγRIII receptors. Infliximab and adalimumab induced ADCC much more potently than etanercept. In the presence of TNF, both mAbs bound C1q in in vitro assays, but etanercept did not bind C1q under any conditions. Infliximab and adalimumab also induced CDC in cells expressing mTNF more potently than etanercept. Differences in the ability to bind ligand and mediate cell death may account for the differences in efficacy and safety of TNF antagonists. 相似文献
195.
Abinav K. Singh Shelly Praveen Bhanu P. Singh Anupam Varma Naveen Arora 《Transgenic research》2009,18(6):877-887
Genetic engineering of food crops has significantly influenced the agricultural productivity over the past two decades. It
has proved a valuable tool, offering crops with higher yields, improved nutritional quality, resistance against pesticides,
herbicides and tolerance against abiotic stresses. However, the safety assessment of genetically engineered (GE) crops is
prerequisite before introduction into human food chain. The present study was aimed to assess the toxicity and allergenicity
of leaf curl virus resistant GE tomato compared to its wild-type species. Balb/c mice fed with genetically engineered or wild-type
tomato did not show significant differences in growth, body weight (P > 0.05) and food consumption when compared with control mice. Values for serum glutamic oxaloacetic transaminase and serum
glutamic pyruvic transaminase, urea and cholesterol were comparable in GE and wild-type tomato fed mice. Mice immunized with
GE or wild-type tomato extract showed low IgE response. Lung histology of ovalbumin fed mice showed bronchoconstriction with
eosinophilic infiltration whereas GE or wild-type tomato showed no cellular infiltration with normal airways. Genetically
engineered and wild-type tomato sensitized mice demonstrated similar IL-4 release in splenic cell culture supernatant. GE
and wild tomato extract on ELISA showed comparable IgE binding (P > 0.05) with food allergic patients’ sera. In conclusion, genetically engineered tomato showed no toxicity in mice and allergenicity
is similar to the wild-type tomato. 相似文献
196.
Yulia Shifrin Pamela D. Arora Yasutaka Ohta David A. Calderwood Christopher A. McCulloch 《Molecular biology of the cell》2009,20(5):1269-1279
Cells in mechanically active environments are subjected to high-amplitude exogenous forces that can lead to cell death. Filamin A (FLNa) may protect cells from mechanically induced death by mechanisms that are not yet defined. We found that mechanical forces applied through integrins enhanced Rac-mediated lamellae formation in FLNa-null but not FLNa-expressing cells. Suppression of force-induced lamella formation was mediated by repeat 23 of FLNa, which also binds FilGAP, a recently discovered Rac GTPase-activating protein (GAP). We found that FilGAP is targeted to sites of force transfer by FLNa. This force-induced redistribution of FilGAP was essential for the suppression of Rac activity and lamellae formation in cells treated with tensile forces. Depletion of FilGAP by small interfering RNA, inhibition of FilGAP activity by dominant-negative mutation or deletion of its FLNa-binding domain, all resulted in a dramatic force-induced increase of the percentage of annexin-V–positive cells. FilGAP therefore plays a role in protecting cells against force-induced apoptosis, and this function is mediated by FLNa. 相似文献
197.
Replication stress often induces chromosome instability. In this study, we explore which factors in replication-compromised
cells promote abnormal chromosome ploidy. We expressed mutant forms of either polymerase α (Polα) or polymerase δ (Polδ) in
normal human fibroblasts to compromise DNA replication. Cells expressing the mutant Polα-protein failed to sustain mitotic
arrest and, when propagated progressively, down-regulated Mad2 and BubR1 and accumulated 4N-DNA from the 2N-DNA cells. Significantly,
a population of these cells became tetraploids. The Polα mutant expressing cells also exhibited elevated cellular senescence
markers, suggesting as a mechanism to limit proliferation of the tetraploids. Expression of the Polδ mutant also caused cells
to accumulate 4N-DNA. In contrast to the Polα mutant expressing cells, the Polδ mutant expressing cells expressed sufficient
levels of Mad2, BubR1, and cyclin B1 to sustain mitotic arrest, and these cells had normal chromosome ploidy. Together, these
results suggest that replication-compromised cells depend on the mitotic checkpoint to prevent mitotic slippage that could
result in tetraploidization. 相似文献
198.
Bioformulation that supports the inoculant under storage condition and on application to field is of prime importance for
agroindustry. Pseudomonas strain EKi having biocontrol activity against Macrophomina phaseolina was used in the study. EKi cells were pretreated by carbon starvation, osmotic stress (NaCl), and freeze drying conditions,
and talc-based bioformulation was developed. Combined pretreatment with carbon starvation and osmotic stress was given to
Pseudomonas cells. Bioformulation of untreated, freeze dried (FD), carbon starved, osmotic stressed, and combined pre-treated cells showed
50.36, 44.76, 45.95, 34.82, and 27.27% reduction in CFU counts after 6 months of storage. The osmotic stressed cells showed
one over-expressed protein (11.5 kDa) in common with carbon starved cells responsible for its better shelf life. The plant
growth promotory activity of bioformulations was determined taking Cicer arietinum as a test crop in M. phaseolina infested field. Carbon starved + osmotic stressed cells showed maximum enhancement of dry weight (272.56%) followed by osmotic
stressed (230.74%), untreated (155.70%), FD (88.93%), and carbon starved (59.34%) cells over uninoculated control. Carbon
starved + osmotic stressed, osmotic stressed, untreated, FD, and carbon starved cells showed 156.60, 100, 75, 40, and 16.67%
reduction of charcoal rot disease over uninoculated control. The results clearly showed that combined pretreatment by carbon
starvation and osmotic stress provides the bacteria potential of rapid adaptation to different environment conditions. 相似文献
199.
Degradation of 2-Chloro-4-nitrophenol (2C4NP) was studied by Arthrobacter sp. SJCon, isolated from the soil of a pesticide contaminated site. This strain utilized 2C4NP as sole source of carbon and
energy and degraded 2C4NP with stoichiometric release of nitrite and chloride ions. A metabolite was detected during the study
of 2C4NP degradation and identified as chlorohydroquinone (CHQ) by thin layer chromatography (TLC), high performance liquid
chromatography (HPLC), and gas chromatography-mass spectrometry (GC–MS). Inhibition study using 2,2′-dipyridyl showed that
CHQ is a terminal aromatic compound in degradation pathway of 2C4NP. CHQ dioxygenase activity was observed in the crude extract
of 2C4NP induced cells of the strain SJCon that suggested the cleavage of the CHQ to maleylacetate (MA). Our study clearly
showed that Arthrobacter sp. SJCon degraded 2C4NP via formation of CHQ that further cleaved to MA by CHQ dioxygenase. This mechanism of degradation
of 2C4NP differs from previously reported degradation pathways of 2C4NP. 相似文献
200.
Qiong Fu Julia Chow Kara A. Bernstein Nodar Makharashvili Sucheta Arora Chia-Fang Lee Maria D. Person Rodney Rothstein Tanya T. Paull 《Molecular and cellular biology》2014,34(5):778-793
In the DNA damage response, many repair and signaling molecules mobilize rapidly at the sites of DNA double-strand breaks. This network of immediate responses is regulated at the level of posttranslational modifications that control the activation of DNA processing enzymes, protein kinases, and scaffold proteins to coordinate DNA repair and checkpoint signaling. Here we investigated the DNA damage-induced oligomeric transitions of the Sae2 protein, an important enzyme in the initiation of DNA double-strand break repair. Sae2 is a target of multiple phosphorylation events, which we identified and characterized in vivo in the budding yeast Saccharomyces cerevisiae. Both cell cycle-dependent and DNA damage-dependent phosphorylation sites in Sae2 are important for the survival of DNA damage, and the cell cycle-regulated modifications are required to prime the damage-dependent events. We found that Sae2 exists in the form of inactive oligomers that are transiently released into smaller active units by this series of phosphorylations. DNA damage also triggers removal of Sae2 through autophagy and proteasomal degradation, ensuring that active Sae2 is present only transiently in cells. Overall, this analysis provides evidence for a novel type of protein regulation where the activity of an enzyme is controlled dynamically by posttranslational modifications that regulate its solubility and oligomeric state. 相似文献