全文获取类型
收费全文 | 1382篇 |
免费 | 93篇 |
国内免费 | 1篇 |
专业分类
1476篇 |
出版年
2022年 | 5篇 |
2021年 | 9篇 |
2020年 | 7篇 |
2019年 | 10篇 |
2018年 | 13篇 |
2017年 | 8篇 |
2016年 | 21篇 |
2015年 | 56篇 |
2014年 | 49篇 |
2013年 | 77篇 |
2012年 | 96篇 |
2011年 | 102篇 |
2010年 | 60篇 |
2009年 | 59篇 |
2008年 | 81篇 |
2007年 | 86篇 |
2006年 | 76篇 |
2005年 | 72篇 |
2004年 | 95篇 |
2003年 | 63篇 |
2002年 | 73篇 |
2001年 | 17篇 |
2000年 | 10篇 |
1999年 | 15篇 |
1998年 | 31篇 |
1997年 | 17篇 |
1996年 | 10篇 |
1995年 | 18篇 |
1994年 | 20篇 |
1993年 | 17篇 |
1992年 | 22篇 |
1991年 | 7篇 |
1990年 | 11篇 |
1989年 | 10篇 |
1988年 | 9篇 |
1987年 | 9篇 |
1986年 | 7篇 |
1985年 | 14篇 |
1984年 | 15篇 |
1983年 | 4篇 |
1982年 | 18篇 |
1981年 | 5篇 |
1980年 | 13篇 |
1979年 | 9篇 |
1978年 | 11篇 |
1977年 | 4篇 |
1976年 | 7篇 |
1975年 | 9篇 |
1974年 | 4篇 |
1961年 | 3篇 |
排序方式: 共有1476条查询结果,搜索用时 15 毫秒
91.
92.
Organellar nuclear-encoded proteins can be mitochondrial, chloroplastic or localized in both mitochondria and chloroplasts. Most of the determinants for organellar targeting are localized in the N-terminal part of the proteins, which were therefore analyzed in Arabidopsis thaliana. The mitochondrial, chloroplastic and dual N-terminal sequences have an overall similar composition. However, Arg is rare in the first 20 residues of chloroplastic and dual sequences, and Ala is more frequent at position 2 of these two types of sequence as compared to mitochondrial sequences. According to these observations, mutations were performed in three dual targeted proteins and analyzed by in vitro import into isolated mitochondria and chloroplasts. First, experiments performed with wild-type proteins suggest that the binding of precursor proteins to mitochondria is highly efficient, whereas the import and processing steps are more efficient in chloroplasts. Moreover, different processing sites are recognized by the mitochondrial and chloroplastic processing peptidases. Second, the mutagenesis approach shows the positive role of Arg residues for enhancing mitochondrial import or processing, as expected by the in silico analysis. By contrast, mutations at position 2 have dramatic and unpredicted effects, either enhancing or completely abolishing import. This suggests that the nature of the second amino acid residue of the N-terminal sequence is essential for the import of dual targeted sequences. 相似文献
93.
Identification of PLOD2 as telopeptide lysyl hydroxylase,an important enzyme in fibrosis 总被引:5,自引:0,他引:5
van der Slot AJ Zuurmond AM Bardoel AF Wijmenga C Pruijs HE Sillence DO Brinckmann J Abraham DJ Black CM Verzijl N DeGroot J Hanemaaijer R TeKoppele JM Huizinga TW Bank RA 《The Journal of biological chemistry》2003,278(42):40967-40972
The hallmark of fibrotic processes is an excessive accumulation of collagen. The deposited collagen shows an increase in pyridinoline cross-links, which are derived from hydroxylated lysine residues within the telopeptides. This change in cross-linking is related to irreversible accumulation of collagen in fibrotic tissues. The increase in pyridinoline cross-links is likely to be the result of increased activity of the enzyme responsible for the hydroxylation of the telopeptides (telopeptide lysyl hydroxylase, or TLH). Although the existence of TLH has been postulated, the gene encoding TLH has not been identified. By analyzing the genetic defect of Bruck syndrome, which is characterized by a pyridinoline deficiency in bone collagen, we found two missense mutations in exon 17 of PLOD2, thereby identifying PLOD2 as a putative TLH gene. Subsequently, we investigated fibroblasts derived from fibrotic skin of systemic sclerosis (SSc) patients and found that PLOD2 mRNA is highly increased indeed. Furthermore, increased pyridinoline cross-link levels were found in the matrix deposited by SSc fibroblasts, demonstrating a clear link between mRNA levels of the putative TLH gene (PLOD2) and the hydroxylation of lysine residues within the telopeptides. These data underscore the significance of PLOD2 in fibrotic processes. 相似文献
94.
95.
To survive in high mountain environments lichens must adapt themselves to alternating periods of desiccation and hydration.
Respiration and photosynthesis of the foliaceous lichen, Xanthoria elegans, in the dehydrated state were below the threshold of CO2-detection by infrared gas analysis. Following hydration, respiration totally recovered within seconds and photosynthesis
within minutes. In order to identify metabolic processes that may contribute to the quick and efficient reactivation of lichen
physiological processes, we analysed the metabolite profile of lichen thalli step by step during hydration/dehydration cycles,
using 31P- and 13C-NMR. It appeared that the recovery of respiration was prepared during dehydration by the accumulation of a reserve of gluconate
6-P (glcn-6-P) and by the preservation of nucleotide pools, whereas glycolytic and photosynthetic intermediates like glucose
6-P and ribulose 1,5-diphosphate were absent. The large pools of polyols present in both X. elegans photo- and mycobiont are likely to contribute to the protection of cell constituents like nucleotides, proteins, and membrane
lipids, and to preserve the integrity of intracellular structures during desiccation. Our data indicate that glcn-6-P accumulated
due to activation of the oxidative pentose phosphate pathway, in response to a need for reducing power (NADPH) during the
dehydration-triggered down-regulation of cell metabolism. On the contrary, glcn-6-P was metabolised immediately after hydration,
supplying respiration with substrates during the replenishment of pools of glycolytic and photosynthetic intermediates. Finally,
the high net photosynthetic activity of wet X. elegans thalli at low temperature may help this alpine lichen to take advantage of brief hydration opportunities such as ice melting,
thus favouring its growth in harsh high mountain climates. 相似文献
96.
CD8 T cell help for innate antitumor immunity 总被引:1,自引:0,他引:1
Shanker A Verdeil G Buferne M Inderberg-Suso EM Puthier D Joly F Nguyen C Leserman L Auphan-Anezin N Schmitt-Verhulst AM 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(10):6651-6662
Innate immunity is considered to initiate adaptive antitumor responses. We demonstrate that monoclonal CD8 T lymphocytes reactive to tumor Ag P1A on P815 mastocytoma cells provide essential "help" to NK cells for rejection of P1A-deficient tumors. RAG-deficient mice have normal NK cells but do not reject either tumor. Reconstitution of these mice with P1A-specific T cells conferred resistance to both P1A-expressing and -deficient tumor cells provided they were present at the same site. Elimination of Ag-negative tumor variants required both activated T and NK cells. Gene expression profiling of NK cells infiltrating P1A-positive tumors in mice with specific CD8 T cells demonstrated an activated effector phenotype. However, CD8 T cell help to NK cells appeared ineffective for P1A-negative variants separated from the P1A-positive tumor. Local tumor Ag-specific T cell-NK cell collaboration results in the elimination of tumor cells whether they express or not the T cell tumor Ag epitope, thus containing the emergence of tumor escape variants before metastasis. 相似文献
97.
98.
99.
Kaloustian S Wann BP Bah TM Falcao S Dufort AM Ryvlin P Godbout R Rousseau G 《Apoptosis : an international journal on programmed cell death》2007,12(11):1945-1951
Reperfused myocardial infarction induces an inflammatory response that is responsible for local and systemic alterations.
Among these, apoptosis observed in the amygdala following myocardial infarction has been pointed out as a consequence of such
an inflammatory process. We hypothesized that inhibition of the inducible inflammatory enzyme Cox-2 during the reperfusion
period may attenuate the apoptotic process in the amygdala. Anaesthetized rats were subjected to left anterior descending
coronary artery occlusion for 40 min, followed by reperfusion. The Cox-2 antagonist Celecoxib (3 mg/kg i.p.) was administered
10 min after the onset of the reperfusion period. After 72 h of reperfusion, infarct size was determined and the lateral and
medial amygdala were dissected from the brain. Infarct size was similar between untreated and Celecoxib-treated animals (40–45%
of the area at risk). Cox-2 expression was significantly reduced in both parts of the amygdala in the Celecoxib group. Apoptosis
regression was observed in the amygdala of the Celecoxib group as shown by decreased number of TUNEL positive cells and by
decreased of caspase-3 activation. Bax/Bcl-2 ratio was not significantly altered by Celecoxib while Akt activation was increased
in the lateral amygdala but not in the medial amygdala. This data indicates that inhibition of Cox-2 by Celecoxib is associated
with regression of apoptosis in the amygdala following myocardial infarction. 相似文献
100.
Marie-Claude Dery Celine Van Themsche Diane Provencher Anne-Marie Mes-Masson Eric Asselin 《Reproductive biology and endocrinology : RB&E》2007,5(1):38-14