全文获取类型
收费全文 | 1366篇 |
免费 | 124篇 |
国内免费 | 1篇 |
专业分类
1491篇 |
出版年
2023年 | 9篇 |
2022年 | 15篇 |
2021年 | 33篇 |
2020年 | 26篇 |
2019年 | 36篇 |
2018年 | 46篇 |
2017年 | 27篇 |
2016年 | 41篇 |
2015年 | 79篇 |
2014年 | 74篇 |
2013年 | 97篇 |
2012年 | 91篇 |
2011年 | 123篇 |
2010年 | 73篇 |
2009年 | 61篇 |
2008年 | 77篇 |
2007年 | 107篇 |
2006年 | 82篇 |
2005年 | 62篇 |
2004年 | 82篇 |
2003年 | 57篇 |
2002年 | 59篇 |
2001年 | 12篇 |
2000年 | 11篇 |
1999年 | 16篇 |
1998年 | 18篇 |
1997年 | 10篇 |
1996年 | 10篇 |
1995年 | 3篇 |
1994年 | 8篇 |
1993年 | 4篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1973年 | 1篇 |
1959年 | 1篇 |
1957年 | 1篇 |
1934年 | 1篇 |
1930年 | 1篇 |
1927年 | 1篇 |
1924年 | 2篇 |
排序方式: 共有1491条查询结果,搜索用时 0 毫秒
81.
SSS Sarma Lynda Beladjal S Nandini Gerardo Cerón-Martínez Karina Tavera-Briseño 《Aquatic biosystems》2005,1(1):1-7
Background
Freshwater anostracans inhabit ephemeral water bodies in which as the water level decreases due to evaporation the salt concentration increases. Thus, for most anostracans salinity becomes the major stress factor.Results
We tested five concentrations of NaCl (0 to 8 g/l) on the life table demography of Branchipus schaefferi fed Chlorella (alga). Age-specific survivorship curves of male and female B. schaefferi showed nearly a similar pattern in that increased salt concentration resulted in decreased survivorship. The age-specific reproduction (mx) of females showed several peaks of cyst production at 0 and 1 g/l salinity while in treatments containing salt at 4 or 8 g/l, there were fewer peaks. Average lifespan, life expectancy at birth, gross and net reproductive rates, generation time and the rate of population increase were all significantly influenced by the salt concentration in the medium. The highest value of net reproductive rate (970 cysts/female) was in treatments containing 0 g/l of salt, while the lowest was 13 cysts/female at 8 g/l. The rate of population increase (r) varied from 0.52 to 0.32 per day depending on the salt concentration in the medium.Conclusion
The low survival and offspring production of B. schaefferi at higher salinity levels suggests that this species is unlikely to colonize inland saline water bodies. Therefore, the temporary ponds in which it is found, proper conservative measures must be taken to protect this species. 相似文献82.
Cameron C Scott Stefania Vossio Fabrizio Vacca Berend Snijder Jorge Larios Olivier Schaad Nicolas Guex Dmitry Kuznetsov Olivier Martin Marc Chambon Gerardo Turcatti Lucas Pelkmans Jean Gruenberg 《EMBO reports》2015,16(6):741-752
The Wnt pathway, which controls crucial steps of the development and differentiation programs, has been proposed to influence lipid storage and homeostasis. In this paper, using an unbiased strategy based on high-content genome-wide RNAi screens that monitored lipid distribution and amounts, we find that Wnt3a regulates cellular cholesterol. We show that Wnt3a stimulates the production of lipid droplets and that this stimulation strictly depends on endocytosed, LDL-derived cholesterol and on functional early and late endosomes. We also show that Wnt signaling itself controls cholesterol endocytosis and flux along the endosomal pathway, which in turn modulates cellular lipid homeostasis. These results underscore the importance of endosome functions for LD formation and reveal a previously unknown regulatory mechanism of the cellular programs controlling lipid storage and endosome transport under the control of Wnt signaling. 相似文献
83.
The purpose of this work was to assess the effect of oligomycin on the mitochondrial membrane permeability transition. The antibiotic was found to strengthen cyclosporin A (CSA)-induced protection of non-specific permeability, which is triggered by a matrix Ca2+ load in the absence of ADP. Oligomycin also reinforced the protective effect of CSA on carboxyatractyloside-induced pore opening in the absence of ADP, but failed to do so in mitochondria incubated under anaerobic conditions or after addition of CCCP. Analyzing the efflux of matrix Ca2+, we found that mitochondrial swelling and the collapse of the transmembrane electric gradient coincided with membrane leakage. The effects of the antibiotic were observed in phosphate-containing media but not in the presence of acetate. Furthermore, N-ethylmaleimide hindered the protective effect of oligomycin-CSA. In addition, the matrix phosphate concentration increased concurrently with a diminution in the matrix-free fraction of Ca2+. We concluded that oligomycin increases phosphate uptake by stimulating the phosphate-/OH- exchange reaction. 相似文献
84.
85.
Phospholipase A2 selectively hydrolyses the ester linkage at the sn-2 position of phospholipids forming lysocompounds. This bioconversion has importance in biotechnology since lysophospholipids are strong bioemulsifiers. The aim of the present work was to study the kinetic behaviour and properties of immobilized phospholipase A2 from bee venom adsorbed into an ion exchange support. The enzyme had high affinity for CM-Sephadex® support and the non-covalent interaction was optimum at pH 8. The activity of immobilized phospholipase A2 was comparatively evaluated with the soluble enzyme using a phospholipid/Triton X-100 mixed micelle as assay system. The immobilized enzyme showed high retention activity and excellent stability under storage. The activity of the immobilized system remained almost constant after several cycles of hydrolysis. Immobilized phospholipase A2 was less sensitive to pH changes compared to soluble form. The kinetic parameters obtained (Vmax 883.4 μmol mg−1 min−1 and a Km 12.9 mM for soluble form and Vmax = 306 μmol mg−1 min−1 and a Km = 3.9 for immobilized phospholipase A2) were in agreement with the immobilization effect. The results obtained with CM-Sephadex®-phospholipase A2 system give a good framework for the development of a continuous phospholipid bioconversion process. 相似文献
86.
González R Wilkerson R Suárez MF García F Gallego G Cárdenas H Posso CE Duque MC 《Memórias do Instituto Oswaldo Cruz》2007,102(3):255-262
The genetic variation and population structure of three populations of Anopheles darlingi from Colombia were studied using random amplified polymorphic markers (RAPDs) and amplified fragment length polymorphism markers (AFLPs). Six RAPD primers produced 46 polymorphic fragments, while two AFLP primer combinations produced 197 polymorphic fragments from 71 DNA samples. Both of the evaluated genetic markers showed the presence of gene flow, suggesting that Colombian An. darlingi populations are in panmixia. Average genetic diversity, estimated from observed heterozygosity, was 0.374 (RAPD) and 0.309 (AFLP). RAPD and AFLP markers showed little evidence of geographic separation between eastern and western populations; however, the F ST values showed high gene flow between the two western populations (RAPD: F ST = 0.029; Nm: 8.5; AFLP: F ST = 0.051; Nm: 4.7). According to molecular variance analysis (AMOVA), the genetic distance between populations was significant (RAPD:phiST = 0.084; AFLP:phiST = 0.229, P < 0.001). The F ST distances and AMOVAs using AFLP loci support the differentiation of the Guyana biogeographic province population from those of the Chocó-Magdalena. In this last region, Chocó and Córdoba populations showed the highest genetic flow. 相似文献
87.
Alicia Santos Savio Osvaldo Reyes Acosta Haydee Gerónimo Pérez Yunier Rodríguez Álvarez Araceli Chico Hilda Garay Pérez Miriam Ojeda Ojeda Celia Aurora Arrieta Aguero Miguel Estévez Gerardo Guillen Nieto 《Journal of peptide science》2012,18(1):25-29
IL‐15 is a proinflammatory cytokine that acts early in the inflammatory response and has been associated with several autoimmune diseases including rheumatoid arthritis, where it had been proposed as a therapeutic target. We recently reported an IL‐15 antagonist peptide corresponding to sequence 36–45 of IL‐15 (KVTAMKCFLL) named P8, which specifically binds to IL‐15Rα and inhibits IL‐15 biological activity with a half maximal inhibitory concentration (IC50) of 130 µ m in CTLL‐2 proliferation assay. In order to improve binding of peptide P8 to the receptor IL‐15Rα, we used an Ala scan strategy to study contribution of each individual amino acid to the peptide's antagonist effect. Here, we found that Phe and Cys are important for peptide binding to IL‐15Rα. We also investigated other single site mutations and replaced the second Lys in the sequence by the polar non‐charged amino acid threonine. The resulting peptide [K6T]P8 exhibited a higher activity than P8 with an IC50 of 24 µm . We also found that this peptide was more active than peptide P8 in the inhibition of TNFα secretion by synovial cells from rheumatoid arthritis patients. The peptide [K6T]P8 described in this work is a new type of IL‐15 antagonist and constitutes a potential therapeutic agent for rheumatoid arthritis. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
88.
Ruiz-Martínez A Vázquez-Juárez E Ramos-Mandujano G Pasantes-Morales H 《Bioscience reports》2011,31(6):489-497
Hypertonicity is a stressful stimulus leading to cell shrinkage and apoptotic cell death. Apoptosis can be prevented if cells are able to activate the mechanism of RVI (regulatory volume increase). This study in mIMCD3 cells presents evidence of a permissive role of the EGFR (epidermal growth factor receptor) on RVI, achieved for the most part through the two main EGFR-triggered signalling chains, the MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) and the PI3K (phosphoinositide 3-kinase)/Akt (also known as protein kinase B) pathways. Hyperosmotic solutions (450 mosM) made by addition of NaCl, increased EGFR phosphorylation, which is prevented by GM6001 and AG1478, blockers respectively, of MMPs (matrix metalloproteinases) and EGFR. Inhibition of EGFR, ERK (PD98059) or PI3K/Akt (wortmannin) phosphorylation reduced RVI by 60, 48 and 58% respectively. The NHE (Na(+)/H(+) exchanger) seems to be the essential mediator of this effect since (i) NHE is the main contributor to RVI, (ii) EGFR, ERK and PI3K/Akt blockers added together with the NHE blocker zoniporide reduce RVI by non-additive effects and (iii) All the blockers significantly lowered the NHE rate in cells challenged by an NH(4)Cl pulse. Besides reducing RVI, the inhibition of MMP, EGFR and PI3K/Akt had a strong pro-apoptotic effect increasing cell death by 2-3.7-fold. This effect was significantly lower when RVI inhibition did not involve the EGFR-PI3K/Akt pathway. These results provide evidence that Akt and its permissive effect on RVI have a predominant influence on cell survival under hypertonic conditions in IMCD3 cells. This role of Akt operates under the influence of EGFR activation, promoted by MMP. 相似文献
89.
In Vitro Stimulation of Protein Kinase C by Melatonin 总被引:2,自引:0,他引:2
Antón-Tay Fernando Ramírez Gerardo Martínez Isabel Benítez-King Gloria 《Neurochemical research》1998,23(5):601-606
It has been shown that melatonin through binding to calmodulin acts both in vitro and in vivo as a potent calmodulin antagonist. It is known that calmodulin antagonists both bind to the hydrophobic domain of Ca2+ activated calmodulin, and inhibit protein kinase C activity. In this work we explored the effects of melatonin on Ca2+ dependent protein kinase C activity in vitro using both a pure commercial rat brain protein kinase C, and a partially purified enzyme from MDCK and N1E-115 cell homogenates. The results showed that melatonin directly activated protein kinase C with a half stimulatory concentration of 1 nM. In addition the hormone augmented by 30% the phorbol ester stimulated protein kinase C activity and increased [3H] PDBu binding to the kinase. In contrast, calmodulin antagonists (500 M) and protein kinase C inhibitors (100 M) abolished the enzyme activity. Melatonin analogs tested were ineffective in increasing either protein kinase C activity or [3H] PDBu binding. Moreover, the hormone stimulated protein kinase C autophosphorylation directly and in the presence of phorbol ester and phosphatidylserine. The results show that besides the melatonin binding to calmodulin, the hormone also interacts with protein kinase C only in the presence of Ca2+. They also suggest that the melatonin mechanism of action may involve interactions with other intracellular hydrophobic and Ca2+ dependent proteins. 相似文献
90.
Gal Bitan Irena Zeltser Gerardo Byk David Halle Yaffa Mashriki Evgenia V. Gluhov Inna Sukhotinsky Menachem Hanani Zvi Selinger Chaim Gilon 《Journal of peptide science》1996,2(4):261-269
Novel backbone-to-side chain and backbone-to-backbone cyclic analogues of substance P (SP) were prepared by solid-phase synthesis and screened for biological activity. An analogue containing a thioether- lactam ring between positions 9 and 11 showed an EC50 value of 20nM toward the neurokinin 1 (NK-1) and was inactive toward the NK-2 and NK-3 receptors. On the other hand, in a multiple backbone cyclic peptide library of similar analogues, in which the sulphur was excluded from the ring, very low activity was detected. The activity was re-evaluated and was found to be even lower (EC50=0.11 mM ) than the previously published data. These results indicate that the thioether moiety has a crucial role in receptor activation. The results also show tolerance of the NK-1 receptor, but not NK-2 or NK-3, to cyclization of the C-terminal portion of the SP6–11 hexapeptide. 相似文献