全文获取类型
收费全文 | 382篇 |
免费 | 34篇 |
国内免费 | 1篇 |
出版年
2024年 | 1篇 |
2022年 | 2篇 |
2021年 | 13篇 |
2020年 | 3篇 |
2019年 | 9篇 |
2018年 | 16篇 |
2017年 | 11篇 |
2016年 | 17篇 |
2015年 | 21篇 |
2014年 | 30篇 |
2013年 | 26篇 |
2012年 | 41篇 |
2011年 | 38篇 |
2010年 | 21篇 |
2009年 | 17篇 |
2008年 | 30篇 |
2007年 | 27篇 |
2006年 | 23篇 |
2005年 | 18篇 |
2004年 | 16篇 |
2003年 | 14篇 |
2002年 | 12篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 2篇 |
1992年 | 1篇 |
1990年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
排序方式: 共有417条查询结果,搜索用时 15 毫秒
21.
22.
Alban Franco Aude Jouaux Michel Mathieu Pascal Sourdaine Christophe Lelong Kristell Kellner Clothilde Heude Berthelin 《Cell and tissue research》2010,340(1):201-210
To understand the processes involved in tissue remodeling associated with the seasonal reproductive cycle of the oyster Crassostrea gigas, we used immunodetection and expression measurements of proliferating cell nuclear antigen (PCNA). The expression of the
PCNA gene was measured by real-time polymerase chain reaction in the whole gonadal area compared with laser microdissected
gonad and storage tissue. Results underlined the advantage of the laser microdissection approach to detect expression, mainly
for early stages of spermatogenesis. In the storage tissue, PCNA expression was reduced in the gonadal tubules, but immunolabeled
hemocytes and vesicular cells were detected when the storage tissue was being restored. In the gonadal tubules, the PCNA gene
was more highly expressed in males than in females. As soon as spermatogenesis was initiated, PCNA expression showed a high
and constant level. In females, the expression level increased gradually until the ripe stage. The immunological approach
established the involvement of peritubular cells in gonadal tubule expansion during early gametogenesis. In both sexes, gonial
mitosis was immunodetected throughout the reproductive cycle. In males, the occurrence of two types of spermatogonia was ascertained
by differential immunolabeling, and intragonadal somatic cell proliferation was noted. As expected, immunolabeling was never
observed from stage II spermatocytes to spermatozoa. In females, positively stained cells were detected from oogonia to growing
oocytes with various labeled intracellular locations. 相似文献
23.
The use of TNF-α antagonists has substantially improved the care of many patients with inflammatory and autoimmune diseases. However, approximately one third of such patients fail to respond well to treatment, regardless of the antagonist used or of the underlying disease. The mechanisms underlying these failures are analyzed in this review, and proposals made concerning how best to adapt therapeutic decisions in these instances. 相似文献
24.
25.
Aurélie Gardarin Stéphane Chédin Gilles Lagniel Jean‐Christophe Aude Emmanuel Godat Patrice Catty Jean Labarre 《Molecular microbiology》2010,76(4):1034-1048
Cadmium (Cd2+) is a very toxic metal that causes DNA damage, oxidative stress and apoptosis. Despite many studies, the cellular and molecular mechanisms underlying its high toxicity are not clearly understood. We show here that very low doses of Cd2+ cause ER stress in Saccharomyces cerevisiae as evidenced by the induction of the unfolded protein response (UPR) and the splicing of HAC1 mRNA. Furthermore, mutant strains (Δire1 and Δhac1) unable to induce the UPR are hypersensitive to Cd2+, but not to arsenite and mercury. The full functionality of the pathways involved in ER stress response is required for Cd2+ tolerance. The data also suggest that Cd2+‐induced ER stress and Cd2+ toxicity are a direct consequence of Cd2+ accumulation in the ER. Cd2+ does not inhibit disulfide bond formation but perturbs calcium metabolism. In particular, Cd2+ activates the calcium channel Cch1/Mid1, which also contributes to Cd2+ entry into the cell. The results reinforce the interest of using yeast as a cellular model to study toxicity mechanisms in eukaryotic cells. 相似文献
26.
27.
Chesnel F Bazile F Pascal A Kubiak JZ 《The International journal of developmental biology》2007,51(4):297-305
Cyclin-dependent kinase 1 (CDK1) is the enzymatic subunit of M-phase Promoting Factor (MPF). It is positively regulated by phosphorylation on Thr-161 and association with a cyclin B molecule. The role of Thr-161 dephosphorylation upon MPF inactivation remains unclear; nevertheless, degradation of cyclin B is thought to be a direct cause of MPF inactivation. However, MPF inactivation actually precedes cyclin B degradation in Xenopus cell-free extracts. Here we study in details the temporal relationship between histone H1 kinase (reflecting MPF activity) inactivation, Thr-161 dephosphorylation, CDK1-cyclin B2 dissociation and cyclin B2 proteolysis in such extracts. We show an asynchrony between inactivation of histone H1 kinase and degradation of cyclin B2. CDK1 dephosphorylation on Thr 161 is an even later event than cyclin B2 degradation, reinforcing the hypothesis that cyclin B dissociation from CDK1 is the key event inactivating MPF. Cyclins synthesized along with MPF inactivation could deliver shortly living active MPF molecules, potentially increasing the asynchrony between histone H1 kinase inactivation and cyclin B2 degradation. We confirm this by showing that in the absence of protein synthesis, such a tendency is lower, but nevertheless, still detectable. Finally, to characterise better CDK1/cyclin B dissociation, we show that CDK1 begins to dissociate from cyclin B2 before the very beginning of cyclin B2 degradation and that the diminution in CDK1-associated cyclin B2 is faster than the decline of its total pool. Thus, neither cyclin B2 degradation nor Thr-161 dephosphorylation participates directly in CDK1 inactivation as measured by histone H1 kinase decline upon the exit from mitotic M-phase in Xenopus embryo extract. 相似文献
28.
Louis H Kakou A Regnault V Labat C Bressenot A Gao-Li J Gardner H Thornton SN Challande P Li Z Lacolley P 《American journal of physiology. Heart and circulatory physiology》2007,293(4):H2597-H2604
We examined the arterial phenotype of mice lacking alpha(1)-integrin (alpha(1)(-/-)) at baseline and after 4 wk of ANG II or norepinephrine (NE) administration. Arterial mechanical properties were determined in the carotid artery (CA). Integrin expression, MAPK kinases, and focal adhesion kinase (FAK) were assessed in the aorta. No change in arterial pressure was observed in alpha(1)(-/-) mice. Elastic modulus-wall stress curves were similar in alpha(1)(-/-) and alpha(1)(+/+) animals, indicating no change in arterial stiffness. The rupture pressure was lower in alpha(1)(-/-) mice, demonstrating decreased mechanical strength. Lack of alpha(1)-integrin was accompanied by an increase in beta(1)-, alpha(v)-, and alpha(5)-integrins but no change in alpha(2)-integrin. ANG II increased medial cross-sectional area of the CA in alpha(1)(+/+), but not alpha(1)(-/-), mice, whereas equivalent pressor doses of NE did not produce a significant increase in either group. In alpha(1)(+/+) mice, ANG II induced alpha(1)-integrin expression and smooth muscle cell (SMC) hypertrophy in the CA in association with increased aortic expression of alpha-smooth muscle actin and smooth muscle myosin heavy chain and phosphorylation of ERK1/2, p38 MAPK, and FAK. ANG II did not induce SMC hypertrophy or phosphorylation of p38 MAPK and FAK in alpha(1)(-/-) mice. A functional anti-alpha(1)-integrin antibody inhibited in vitro the ANG II-induced phosphorylation of FAK and p38 MAPK. In conclusion, alpha(1)(-/-) mice exhibit a reduced mechanical strength at baseline and a lack of ANG II-induced SMC hypertrophy. These results emphasize the importance of alpha(1)beta(1)-integrin in p38 MAPK and FAK phosphorylation during vascular hypertrophy in response to ANG II. 相似文献
29.
30.
Aude Vialatte Manuel Plantegenest Jean‐Christophe Simon Charles‐Antoine Dedryver 《Agricultural and Forest Entomology》2007,9(4):337-346
1 Integrated management of crop pests requires the identification of the appropriate spatial scale at which colonization processes occurs. We assessed, by coupling demographic and genetic methods, the relative contribution of local and transient migrants of the grain aphid Sitobion avenae to wheat field colonization in spring. 2 We examined, during two consecutive years, the daily colonization of wheat by aphid migrants and compared this with daily aphid flight monitored by a local 12.2‐m suction trap. The genetic profiles of aphids landing on crops were compared with those of both flying aphids caught by the suction trap and local populations from arable crops and hedgerows. 3 In the first year, we observed: (i) a strong correlation between aphids colonizing the crop and those moving within the crop and a close genetic similarity between aphids from these samples and (ii) a high level of genetic differentiation between these aphids and populations from local cereals and field margins. In the second year, the number of migrants recorded on the wheat was three‐fold higher than in the previous year, and less correlated with that recorded by the suction trap. This was associated with a lack of genetic differentiation between all samples. 4 This variation in the colonization processes resulted mainly in an abrupt increase in abundance of genotypes from local over‐wintering sites in 2004. This suggests that, despite the long range dispersal potential of the grain aphid, outbreak risks could be mainly determined at a local scale, encouraging the design of relatively small management units. 相似文献