全文获取类型
收费全文 | 4502篇 |
免费 | 259篇 |
国内免费 | 15篇 |
专业分类
4776篇 |
出版年
2024年 | 6篇 |
2023年 | 46篇 |
2022年 | 88篇 |
2021年 | 108篇 |
2020年 | 81篇 |
2019年 | 109篇 |
2018年 | 155篇 |
2017年 | 113篇 |
2016年 | 183篇 |
2015年 | 245篇 |
2014年 | 263篇 |
2013年 | 314篇 |
2012年 | 389篇 |
2011年 | 446篇 |
2010年 | 235篇 |
2009年 | 221篇 |
2008年 | 251篇 |
2007年 | 262篇 |
2006年 | 187篇 |
2005年 | 168篇 |
2004年 | 134篇 |
2003年 | 119篇 |
2002年 | 112篇 |
2001年 | 73篇 |
2000年 | 70篇 |
1999年 | 55篇 |
1998年 | 39篇 |
1997年 | 32篇 |
1996年 | 19篇 |
1995年 | 29篇 |
1994年 | 18篇 |
1993年 | 16篇 |
1992年 | 14篇 |
1991年 | 14篇 |
1990年 | 18篇 |
1989年 | 23篇 |
1988年 | 16篇 |
1987年 | 13篇 |
1986年 | 11篇 |
1985年 | 9篇 |
1984年 | 14篇 |
1983年 | 5篇 |
1979年 | 9篇 |
1978年 | 5篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1971年 | 5篇 |
1969年 | 3篇 |
排序方式: 共有4776条查询结果,搜索用时 15 毫秒
131.
CD38, a multifunctional enzyme that catalyzes the synthesis of intracellular Ca(2+) messengers, cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP), is known to be expressed on platelets. However, the role of CD38 in platelets remains unclear. Our present results show that treatment of platelets with thrombin results in a rapid and sustained Ca(2+) signal, resulting from a coordinated interplay of Ca(2+)-mobilizing messengers, inositol 1,4,5-trisphosphate, cADPR, and NAADP. By dissecting the signaling pathway using various agents, we delineated that cADPR and NAADP are sequentially produced through CD38 internalization by protein kinase C via myosin heavy chain IIA following phospholipase C activation in thrombin-induced platelets. An inositol 1,4,5-trisphosphate receptor antagonist blocked the thrombin-induced formation of cADPR and NAADP as well as Ca(2+) signals. An indispensable response of platelets relying on cytosolic calcium is the surface exposure of phosphatidylserine (PS), which implicates platelet procoagulant activity. Scrutinizing this parameter reveals that CD38(+/+) platelets fully express PS on the surface when stimulated with thrombin, whereas this response was decreased on CD38(-/-) platelets. Similarly, PS exposure and Ca(2+) signals were attenuated when platelets were incubated with 8-bromo-cADPR, bafilomycin A1, and a PKC inhibitor. Furthermore, in vivo, CD38-deficient mice exhibited longer bleeding times and unstable formation of thrombus than wild type mice. These results demonstrate that CD38 plays an essential role in thrombin-induced procoagulant activity of platelets and hemostasis via Ca(2+) signaling mediated by its products, cADPR and NAADP. 相似文献
132.
Sun P Maloney KN Nam SJ Haste NM Raju R Aalbersberg W Jensen PR Nizet V Hensler ME Fenical W 《Bioorganic & medicinal chemistry》2011,19(22):6557-6562
Three new depsipeptides, fijimycins A-C (1-3), together with the known etamycin A (4), were isolated and identified from the fermentation broth of strain CNS-575, a Streptomyces sp. cultured from a marine sediment sample collected off Nasese, Fiji. The planar structures of the new fijimycins were assigned by combined interpretation of NMR and MS/MS spectroscopic data. These assignments were complicated by the fact that 1-3 occurred as complex amide conformational mixtures. The absolute configurations of the component amino acids were established using the Marfey's method. Fijimycins A-C, and etamycin A, were shown to possess significant in vitro antibacterial activity against three methicillin-resistant Staphylococcus aureus (MRSA) strains with MIC(100) values between 4 and 16 μg mL(-1). 相似文献
133.
134.
Summary A simple method is proposed for calculating oxygen pentration depth in immobilized cells by assuming zero order kinetics in the presence of several external oxygen transport resistances. Calculations indicate that typical penetration depths of oxygen for immobilized microbial cells are in the range of 50–200 and those for immobilized or encapsulated animal and plant tissue culture are about 500–1000 . Based on calculations, oxygen transport in microencapsulation and microcarriers for tissue cultures are not transport-limited, but a slight limitation is expected for those in a hollow fiber reactor.Nomenclature as
specific area of a support (cm)
- Bi
Biot number
-
dimensionless
- Cb
oxygen concentration in the bulk liquid (mM)
-
C
b
C
b
*
-Ccr (mM)
- C
b
*
bulk oxygen concentration in equilibrium with air (mM)
- Ccr
critical oxygen concentration (mM)
- Cs
oxygen concentration in the solid phase (mM)
- dp
diameter or thickness of a support (cm)
- Deff
effective diffusivity of oxygen in the solid phase (cm2/s)
- km
membrane permeability of oxygen (cm/s)
- k
m
*
Deff/m
- kLaL
liquid phase mass transfer rate coefficient (1/s)
- ksas
solid phase mass transfer rate coefficient (1/s)
- (OUR)v
volumetric oxygen uptake rate (mmol O2/l)
- p
geometry parameter, p=0 for slab, p=1 for cylinder, p=2 for sphere
- Pd
oxygen penetration depth (cm)
-
P
d
oxygen penetration depth in the absence of external diffusion limitation (cm)
- Q
volumetric oxygen uptake rate,
(mmol O2/l·h)
-
specific oxygen uptake rate (mmol O2gm biomass (dry)·h)
- r
length coordinate (cm)
- rc
oxygen penetration depth for sphere (cm)
-
r
c
rc in the absence of external diffusion limitation (cm)
- r
c
*
oxygen penetration depth for cylinder (cm)
-
r
c
*
r
c
*
in the absence of external diffusion limitation (cm)
- rcom
combined mass transfer rate resistance (s)
- rd
location where Cs becomes zero or Ccr (cm)
- ri
radius of cylinder or sphere, half thickness of slab (cm)
- Usg
superficial gas velocity (cm/s)
- X
cell concentration (g/l)
Greek letters
Thiele modulus, dimensionless
- L, s
liquid and solid phase volume fraction, respectively, dimensionless
-
effectiveness factor
On sabbatical leave from KAIST, Seoul, Korea 相似文献
135.
Hierarchical Zn–Co–S Nanowires as Advanced Electrodes for All Solid State Asymmetric Supercapacitors 下载免费PDF全文
A facile two‐step strategy is developed to design the large‐scale synthesis of hierarchical, unique porous architecture of ternary metal hydroxide nanowires grown on porous 3D Ni foam and subsequent effective sulfurization. The hierarchical Zn–Co–S nanowires (NWs) arrays are directly employed as an electrode for supercapacitors application. The as‐synthesized Zn–Co–S NWs deliver an ultrahigh areal capacity of 0.9 mA h cm?2 (specific capacity of 366.7 mA h g?1) at a current density of 3 mA cm?2, with an exceptional rate capability (≈227.6 mA h g?1 at a very high current density of 40 mA cm?2) and outstanding cycling stability (≈93.2% of capacity retention after 10 000 cycles). Most significantly, the assembled Zn–Co–S NWs//Fe2O3@reduced graphene oxide asymmetric supercapacitors with a wide operating potential window of ≈1.6 V yield an ultrahigh volumetric capacity of ≈1.98 mA h cm?3 at a current density of 3 mA cm?2, excellent energy density of ≈81.6 W h kg?1 at a power density of ≈559.2 W kg?1, and exceptional cycling performance (≈92.1% of capacity retention after 10 000 cycles). This general strategy provides an alternative to design the other ternary metal sulfides, making it facile, free‐standing, binder‐free, and cost‐effective ternary metal sulfide‐based electrodes for large‐scale applications in modern electronics. 相似文献
136.
Eun-Joo Kim Chang-Won Kang Nan-Hee Kim Yong Bae Seo Soo-Wan Nam Gun-Do Kim 《Biotechnology and Bioprocess Engineering》2018,23(2):201-207
Loranthus yadoriki, one of the Korean mistletoe species, has been already known for anti-viral effects, but the molecular basis that it caused apoptosis in cancer cells was not definitely revealed yet. The aim of this study was to estimate the mechanisms of apoptotic cell death of the extract from Loranthus yadoriki (named as ELY) in human cervix HeLa cells. We identified that ELY prevented the proliferation of HeLa cells between 50 and 300 μg/mL which did not affect non-cancerous HaCaT cells. In addition, ELY induced a morphological change and nucleus disruption as well as an accumulation of sub-G1 phase in HeLa cells. The mechanism study, by using western blot analysis, showed that the phosphorylation of Fas-associated death domain (FADD), Bim and Bak was up-regulated by ELY treatment. Furthermore, the expression of cytochrome c and Apaf-1 was increased by ELY treatment. In immunofluorescence staining, the increased intensity of cleaved caspase-3 and cleaved PARP was also observed under ELY treatment. Sequentially, the caspase cascade was activated by ELY from caspase-8 to caspase-3 and from caspase-9 to caspase-3, in both extrinsic and intrinsic pathways. The results of this study demonstrate that ELY has anti-cancer effects on human cervix cancer HeLa cells via caspase cascade in apoptotic signaling pathways. 相似文献
137.
Nam Hoai Nguyen Jung-Rae Kim Sunghoon Park 《Biotechnology and Bioprocess Engineering》2018,23(5):564-572
Application of the recently developed wholecell 3-HP biosensor, which detects 3-hydroxypropionic acid (3-HP) and expresses fluorescence as an output signal in response to the 3-HP concentration, was studied in three areas of enzyme and metabolic engineering. First, a sensor was applied to identify active 3-hydroxyaldehyde dehydrogenase (ALDH), a key enzyme in the 3-HP production pathway. Second, with the aid of helper enzymes that catalyze the conversion of 1,3-propanediol (1,3-PDO) to 3-HP, a 3-HP biosensor was converted into a 1,3-PDO biosensor. Third, a 3-HP biosensor, with proper modifications in expression module of the output signal and the use of pH-tolerant red fluorescent protein (RFP), was shown to monitor the rate of 3-HP production under process conditions in which one or more interfering compounds are present in the culture medium and/or the medium pH decreases. This study demonstrates that 3-HP biosensors can be widely used in enzyme and metabolic engineering applications for 3-HP production. 相似文献
138.
Under intensive environmental stress, reported that plants have complementary and positive interactions instead of competition among species. In order to examine whether there as a possible correlation between the performance of Halenia corniculata and the coverage/height of other plants with the same distribution, a total of 30 plots were established at two representative distributional areas. The height, total number of chasmogamous flowers and cleistogamous flowers, their overall plots coverage, and observed plants species on each plot were determined. Our results revealed that the number of chasmogamous and cleistogamous flowers of Halenia corniculata was increased when its height was increased. The performance of Halenia corniculata was found to have a significant correlation with the overall coverage of observed plants species in the plot as well as the height of observed plants in established plots. Our results suggest that the biennial plant Halenia corniculata might be able to choose a site inhabited by other perennial plants in the high-altitude region under environmental stress for appropriate growth and reproduction. One main reason that Halenia corniculata seedlings could be established in regions where other plants are inhabited might be due to the degree of light requirement by the seedling stage is different from that at the adult stage. The size of Halenia corniculata population in South Korea was found to be proportional to that of available sites that could support its life cycle, suggesting that available sites need to be secure in order to maintain its life cycle. 相似文献
139.
Different fermentation strategies by Schizochytrium mangrovei strain pq6 to produce feedstock for exploitation of squalene and omega‐3 fatty acids 下载免费PDF全文
Thom Thi Le Thi Huong Quynh Hoang Van Nhat Pham Minh Hien Thi Hoang Hoai Thu Thi Ngo Dang Diem Hong 《Journal of phycology》2018,54(4):550-556
Schizochytrium mangrovei strain PQ 6 was investigated for coproduction of docosahexaenoic acid (C22: 6ω‐3, DHA ) and squalene using a 30‐L bioreactor with a working volume of 15 L under various batch and fed‐batch fermentation process regimes. The fed‐batch process was a more efficient cultivation strategy for achieving higher biomass production rich in DHA and squalene. The final biomass, total lipid, unsaponifiable lipid content, and DHA productivity were 105.25 g · L?1, 43.40% of dry cell weight, 8.58% total lipid, and 61.66 mg · g?1 · L?1, respectively, after a 96 h fed‐batch fermentation. The squalene content was highest at 48 h after feeding glucose (98.07 mg · g?1 of lipid). Differences in lipid accumulation during fermentation were correlated with changes in ultrastructure using transmission electron microscopy and Nile Red staining of cells. The results may be of relevance to industrial‐scale coproduction of DHA and squalene in heterotrophic marine microalgae such as Schizochytrium . 相似文献
140.
Won Yong Jung Haneul Kim Se Jin Jeon Hye Jin Park Hyuck Jai Choi Nam Jae Kim Dong Hyun Kim Dae Sik Jang Jong Hoon Ryu 《Neurochemical research》2018,43(2):351-362
Eclalbasaponin II derived from Eclipta prostrata L. (Asteraceae) has been reported to have anti-fibrotic, anti-bacterial and autophagic activities, but its effect on cognitive function has not been investigated. We studied the effect of eclalbasaponin II on cholinergic blockade-induced memory impairment in mice using the passive avoidance, Y-maze, and Morris water maze tasks. Eclalbasaponin II (10 or 20 mg/kg, p.o.) significantly ameliorated the cognitive dysfunction induced by scopolamine in the passive avoidance, Y-maze, and the Morris water maze tasks. To identify the mechanism of the memory-ameliorating effect of eclalbasaponin II, acetylcholinesterase (AChE) activity assay, Western blot analysis and electrophysiology were conducted. Eclalbasaponin II inhibited the AChE activity in ex vivo study, and the administration of eclalbasaponin II and its metabolite, echinocystic acid, increased the phosphorylation levels of memory-related signaling molecules, including protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β), in the hippocampus. Although eclalbasaponin II did not affect hippocampal long term potentiation (LTP), echinocystic acid significantly enhanced hippocampal LTP formation (30 μM). These results suggest that eclalbasaponin II ameliorates cholinergic blockade-induced cognitive impairment via AChE inhibition, LTP formation and the activation of Akt-GSK-3β signaling, and that eclalbasaponin II may be a useful to treat cognitive impairment derived from cholinergic dysfunction. 相似文献