全文获取类型
收费全文 | 13642篇 |
免费 | 1235篇 |
国内免费 | 730篇 |
出版年
2024年 | 39篇 |
2023年 | 351篇 |
2022年 | 414篇 |
2021年 | 763篇 |
2020年 | 783篇 |
2019年 | 1026篇 |
2018年 | 756篇 |
2017年 | 458篇 |
2016年 | 531篇 |
2015年 | 678篇 |
2014年 | 938篇 |
2013年 | 1123篇 |
2012年 | 663篇 |
2011年 | 803篇 |
2010年 | 543篇 |
2009年 | 646篇 |
2008年 | 635篇 |
2007年 | 624篇 |
2006年 | 568篇 |
2005年 | 492篇 |
2004年 | 433篇 |
2003年 | 400篇 |
2002年 | 322篇 |
2001年 | 168篇 |
2000年 | 149篇 |
1999年 | 138篇 |
1998年 | 118篇 |
1997年 | 91篇 |
1996年 | 95篇 |
1995年 | 81篇 |
1994年 | 64篇 |
1993年 | 70篇 |
1992年 | 59篇 |
1991年 | 47篇 |
1990年 | 41篇 |
1989年 | 33篇 |
1988年 | 38篇 |
1987年 | 34篇 |
1986年 | 41篇 |
1985年 | 43篇 |
1984年 | 70篇 |
1983年 | 41篇 |
1982年 | 54篇 |
1981年 | 35篇 |
1980年 | 29篇 |
1979年 | 21篇 |
1978年 | 13篇 |
1977年 | 12篇 |
1976年 | 9篇 |
1974年 | 6篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
91.
Wouter J. Middelhoven Alex Coenen Bart Kraakman Maarten D. Sollewijn Gelpke 《Antonie van Leeuwenhoek》1992,62(3):181-187
The imperfect ascomycetous yeastsCandida parapsilosis andArxula adeninivorans degraded 3-hydroxybenzoic acid via gentisate which was the cleavage substrate. 4-Hydroxybenzoic acid was metabolized via protocatechuate. No cleavage enzyme for the latter was detected. In stead of this NADH- and NADPH-dependent monooxygenases were present. In cells grown at the expense of hydroquinone and 4-hydroxygenzoic acid, enzymes of the hydroxyhydroquinone variant of the 3-oxoadipate pathway were demonstrated, which also took part in the degradation of 2,4-dihydroxybenzoic acid byC. parapsilosis.Abbreviations HHQ
Hydroxyhydroquinone (1,2,4-trihydroxybenzene)
- GSH
reduced Glutathione 相似文献
92.
Wim van Uden Niesko Pras Esther M. Vossebeld Jos N. M. Mol Theo M. Malingré 《Plant Cell, Tissue and Organ Culture》1990,20(2):81-87
Cell suspension cultures of Linum flavum L., routinely grown on a NAA-containing medium, accumulated low levels of the phenylpropanoid-derived lignan 5-methoxypodophyllotoxin (5-MPT), up to 0.004% on a dry weight basis. Feeding experiments with the precursor L-phenylalanine resulted in a 3–5-fold increase in 5-MPT levels, but caused the levels of PAL activity to fall. Treatment of the cultures with the elicitor Nigeran, either alone or in combination with phenylalanine, caused the 5-MPT production to cease, even though PAL activity was rapidly enhanced by these treatments. Transfer of the cultures to NAA-free medium resulted in a 40–50 fold higher level of 5-MPT accumulation, the PAL activity levels being lowered compared to the routinely grown cells. With these more differentiated cultures, phenylalanine feeding and elicitor treatment, both on its own and in combination with the precursor, had no effect on 5-MPT production, even though the PAL activity levels were higher than in the untreated cells. It can be concluded that in lignan-accumulating cultures of L. flavum, PAL activity is nearly always detectable and seems to show a reciprocal relationship with 5-MPT accumulation.Abbreviations 5-MPT
5-methoxypodophyllotoxin
- PAL
phenylalanine ammonia lyase (EC 4:3:1.5)
- NAA
naphthaleneacetic acid 相似文献
93.
The green alga Chlamydomonas reinhardtii is a facultative heterotroph and, when cultured in the presence of acetate, will synthesize chlorophyll (Chl) and photosystem (PS) components in the dark. Analysis of the thylakoid membrane composition and function in dark grown C. reinhardtii revealed that photochemically competent PS II complexes were synthesized and assembled in the thylakoid membrane. These PS II centers were impaired in the electron-transport reaction from the primary-quinone electron acceptor, QA, to the secondary-quinone electron acceptor, QB (QB-nonreducing centers). Both complements of the PS II Chl a–b light harvesting antenna (LHC II-inner and LHC II-peripheral) were synthesized and assembled in the thylakoid membrane of dark grown C. reinhardtii cells. However, the LHC II-peripheral was energetically uncoupled from the PS II reaction center. Thus, PS II units in dark grown cells had a -type Chl antenna size with only 130 Chl (a and b) molecules (by definition, PS II units lack LHC II-peripheral). Illumination of dark grown C. reinhardtii caused pronounced changes in the organization and function of PS II. With a half-time of about 30 min, PS II centers were converted froma QB-nonreducing form in the dark, to a QB-reducing form in the light. Concomitant with this change, PS II units were energetically coupled with the LHC II-peripheral complement in the thylakoid membrane and were converted to a PS II form. The functional antenna of the latter contained more than 250 Chl(a+b) molecules. The results are discussed in terms of a light-dependent activation of the QA-QB electron-transfer reaction which is followed by association of the PS II unit with a LHC II-peripheral antenna and by inclusion of the mature form of PS II (PS II) in the membrane of the grana partition region.Abbreviations Chl
chlorophyll
- PS
photosystem
- QA
primary quinone electron acceptor of PS II
- QB
secondary quinone electron acceptor of PS II
- LHC
light harvesting complex
- F0
non-variable fluorescence yield
- Fplf
intermediate fluorescence yield plateau leyel
- Fmax
maximum fluorescence yield
- Fi
initial fluorescence yield increase from F0 to Fpl (Fpl–F0)
- Fv
total variable fluorescence yield (Fm–F0)
- DCMU
dichlorophenyl-dimethylurea 相似文献
94.
Bernhard Hoffmann Isolde Nagel Wolfgang Clauss 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1990,160(4):381-388
Summary Regulation of the paracellular pathway in rabbit distal colon by the hormone aldosterone was investigated in vitro in Ussing chambers by means of transepithelial and microelectrode techniques. To evaluate the cellular and paracellular resistances an equivalent circuit analysis was used. For the analysis the apical membrane resistance was altered using the antibiotic nystatin. Under control conditions two groups of epithelia were found, each clearly dependent on the light: dark regime. Low-transporting epithelia (LT) were observed in the morning and high-transporting epithelia (HT) in the afternoon. Na+ transport was about 3-fold higher in HT than in LT epithelia. Incubating epithelia of both groups with 0.1 mol·1-1 aldosterone on the serosal side nearly doubled in LT epithelia the short circuit current and transepithelial voltage but the transepithelial resistance was not influenced. Maximal values were reached after 4–5 h of aldosterone treatment. In HT epithelia due to the effect of aldosterone all three transepithelial parameters remained constant over time. Evaluation of the paracellular resistance revealed a significant increase after aldosterone stimulation in both epithelial groups. This increase suggests that tight junctions might have been regulated by aldosterone. The hormonal effect on electrolyte transport was also dependent on the physiological state of the rabbit colon. Since net Na+ absorption in distal colon is, in addition to transcellular absorption capacity, also dependent on the permeability of the paracellular pathway, the regulation of tight junctions by aldosterone may be a potent mechanism for improving Na+ absorption during hormone-stimulated ion transport.Abbreviations
V
t
transepithelial potential difference (mV)
-
R
t
transepithelial resistance (·cm2)
-
G
t
transepithelial conductance (mS·cm-2)
- Isc
calculated short circuit current (A·cm-2)
-
V
a
apical membrane potential difference (mV)
-
V
bl
basolateral membrane potential difference (mV)
-
voltage divider ratio
-
R
a
apical membrane resistance (·cm2)
-
R
bl
basolateral membrane resistance (·cm2)
-
R
c
cellular resistance ( of apical and basolateral resistance) (·cm2)
-
R
p
resistance of the paracellular pathway (·cm2)
-
G
a
apical membrane conductance (mS·cm-2)
-
G
bl
basolateral membrane conductance (mS·cm-2)
-
G
p
paracellular conductance (mS·cm-2)
-
G
t
transepithelial conductance (mS·cm-2)
-
HT
contr
high transporting control epithelia
-
LT
contr
low transporting control epithelia
-
HT
aldo
aldosterone incubated high transporting epithelia
-
LT
aldo
aldosterone incubated low transporting epithelia 相似文献
95.
Kimberlee K. Wallace Gregory F. Payne Marilyn K. Speedie 《Journal of industrial microbiology & biotechnology》1990,6(1):43-48
Summary A defined medium containing glucose and ammonium as the sole carbon and nitrogen sources was developed to support growth and streptonigrin production. In this defined medium, increased initial levels of ammonium resulted in increased growth suggesting that nitrogen is the growth limiting nutrient. In some cases, increased initial ammonium levels resulted in decreased specific streptonigrin productivity, suggesting that nitrogen regulatory mechanisms may adversely affect streptonigrin biosynthesis. This suggestion that nitrogen regulation adversely affects antibiotic biosynthesis is further supported by results from two studies in which the ammonium supply to the cells was controlled. In the first study, streptonigrin productivity and final titer were enhanced by the addition of an ammonium trapping agent. In the second experiment, when ammonium chloride was fed slowly throughout the course of cultivation, the production phase was lengthened and the maximum antibiotic concentration was enhanced compared to the batch controls containing either the same initial or the same total ammonium chloride levels. Although our results indicate streptonigrin production may be subject to nitrogen regulatory mechanisms, the effect of nitrogen on streptonigrin production cannot be strictly correlated to the extracellular ammonium concentration. In fact, we observed that when ammonium was depleted from the medium, streptonigrin production ceased. 相似文献
96.
Y.-H. Tai J. Flick S.A. Levine J.L. Madara G.W.G. Sharp M. Donowitz 《The Journal of membrane biology》1996,149(1):71-79
Elevation in intracellular Ca2+ acting via protein kinase C (PKC) is shown to regulate tight junction resistance in T84 cells, a human colon cancer line and a model Cl− secretory epithelial cell. The Ca2+ ionophore A23187, which was used to increase the intracellular Ca2+ concentration, caused a decrease in tight junction resistance in a concentration- and time-dependent manner. Dual Na+/mannitol serosal-to-mucosal flux analysis performed across the T84 monolayers treated with 2 μm A23187 revealed that A23187 increased both fluxes and that in the presence of ionophore there was a linear relationship between
the Na+ and mannitol fluxes with a slope of 56.4, indicating that the decrease in transepithelial resistance was due to a decrease
in tight junction resistance. Whereas there was no effect of 0.1 μm A23187, 1 or 2 μm produced a 55% decrease in baseline resistance in 1 hr and 10 μm decreased resistance more than 80%. The A23187-induced decrease in tight junction resistance was partially reversible by
washing 3 times with a Ringer's-HCO3 solution containing 1% BSA. The A23187 effect on resistance was dependent on intracellular Ca2+; loading the T84 cells with the intracellular Ca2+ chelator BAPTA significantly reduced the decrease in tight junction resistance caused by A23187. This intracellular Ca2+ effect was mediated by protein kinase C and not calmodulin. While the protein kinase C antagonist H-7 totally prevented the
action of A23187 on tight junction resistance, the Ca2+/calmodulin inhibitor W13 did not have any effect. Sphingosine, another inhibitor of PKC, partially reduced the A23187-induced
decline in tight junction resistance. The PKC agonist PMA mimicked the A23187 effect on resistance, although the effect was
delayed up to 1 hr after exposure. In addition, however, PMA also caused an earlier increase in resistance, indicating it
had an additional effect in addition to mimicking the effect of elevating Ca2+. The effects of a phospholipase inhibitor (mepacrine) and of inhibitors of arachidonic acid metabolism (indomethacin for
the cyclooxygenase pathway, NDGA for the lipoxygenase pathway, and SKF 525A for the epoxygenase pathway) on the A23187 action
were also examined. None of these agents altered the A23187-induced decrease in resistance. Monolayers exposed to 2 μm A23187 for 1 hr were stained with fluorescein conjugated phalloidin, revealing that neighboring cells did not part one from
another and that A23187 did not have a detectable effect on distribution of F-actin in the perijunctional actomyosin ring.
The results indicate that elevation in intracellular Ca2+ decreases tight junction resistance in the T84 monolayer, acting through protein kinase C by a mechanism which does not involve visible changes in the perijunctional actomyosin
ring.
Received: 14 July 1995/Revised: 25 September 1995 相似文献
97.
E.V. Sviderskaya E. Jazrawi S.A. Baldwin C.C. Widnell C.A. Pasternak 《The Journal of membrane biology》1996,149(2):133-140
The stimulation of glucose transport in response to various types of stress has been studied. There is no relationship between
effects of stress-inducing agents on glucose transport and their effects on cellular protein synthesis. Although the effect
of stress on glucose transport appears analogous to its stimulation by insulin, cells that are slightly insulin-sensitive
in terms of glucose transport (BHK cells) show a similar degree of stimulation as highly insulin-sensitive cells (differentiated
3T3-L1 cells). External labeling of the transporter protein with a photoactivatable derivative of mannose, 2-N-4-(1-azi-2,2,2-trifluoroethyl)
benzoyl-1, 3-bis-(D-mannos-4-yloxy)-propylamine, shows that most of the increased glucose transport activity correlates with
an increase in the amount of the transporter on the cell surface. Cells subjected to K+-depletion, which inhibits endocytosis and results in an accumulation of receptors at the cell surface, show the same increase
in glucose transport as cells exposed to stress; stressed cells show no further increase in glucose transport when subjected
to K+ depletion. These results support the view (Widnell, C.C., Baldwin, S.A., Davies, A., Martin, S., Pasternak, C.A. 1990. FASEB J
4:1634–1637) that cellular stress increases glucose transport by promoting the accumulation of glucose transporter molecules
at the cell surface.
Received: 20 June 1995/Revised: 29 September 1995 相似文献
98.
P. J. Flor J. Gomeza M. A. Tones R. Kuhn J.-P. Pin T. Knöpfel 《Journal of neurochemistry》1996,67(1):58-63
Abstract: The metabotropic glutamate receptor (mGluR) subtype 1 exists as at least three variants (−1a, −1b, and −1c) generated by alternative splicing at the C-terminal domain. Fluorometric Ca2+ measurements were used to compare the concentration dependency of agonist-induced rises in intracellular free Ca2+ concentration ([Ca2+ ]i ) in human embryonic HEK 293 cells transiently expressing rat mGluR1a, mGluR1b, or mGluR1c. The rank order of agonist potencies was quisqualate ≫ (2 S, 1' S, 2' S )-2-(carboxycyclopropyl)glycine (L-CCG-I) > (1 S, 3 R )-1-aminocyclopentane-1,3-dicarboxylic acid [(1 S, 3 R )-ACPD] and did not differ among the splice variants. However, agonists were consistently more potent at mGluR1a than at mGluR1c and mGluR1b. In the same system, we characterized the agonist pharmacology of two chimeric rat mGluR3/1 receptors where the first and/or the second intracellular loop(s) and the C-terminal domain were exchanged with the corresponding mGluR1a or mGluR1c sequences and that were previously shown to mediate elevations in [Ca2+ ]i in response to agonists. The potency of agonists was higher at the chimera having the C-terminus of mGluR1a as compared with those having the mGluR1c C-terminus. Both chimeric mGluR3/1 receptors had the same rank order of agonist potencies: L-CCG-I ≫ (1 S, 3 R )-ACPD ∼ quisqualate. These data support the hypothesis that the C-terminal domain of mGluRs plays a role in determining the potency of agonists for inducing mGluR-mediated functional responses. 相似文献
99.
Protein Tyrosine Kinase-Mediated Potentiation of Currents from Cloned NMDA Receptors 总被引:13,自引:8,他引:5
Abstract: Although serine/threonine phosphorylation has been more commonly recognized as a mechanism to modulate the function of ion channels and receptors, tyrosine phosphorylation is under increasing scrutiny. An important subtype of glutamate receptor, the NMDA receptor, is shown to be regulated by insulin via protein tyrosine kinase (PTK). NMDA currents through cloned receptors are potentiated by insulin in a subunit-specific manner. The insulin-mediated potentiation of NMDA current is diminished by inhibitors of PTKs. At least one exogenous cytosolic PTK, pp60c- src , is also able to potentiate NMDA current. Because later application of PTK inhibitors can reverse the seemingly stable insulin-mediated potentiation of NMDA current, it appears that tyrosine residues responsible for potentiation are continually rephosphorylated by some long-term PTK activity that was induced via insulin treatment. 相似文献
100.
Extracellular Striatal Dopamine and Glutamate After Decortication and Kainate Receptor Stimulation, as Measured by Microdialysis 总被引:5,自引:3,他引:2
I. Smolders S. Sarre C. Vanhaesendonck G. Ebinger Y. Michotte 《Journal of neurochemistry》1996,66(6):2373-2380
Abstract: Disruption of corticostriatal glutamate input in the striatum decreased significantly extracellular striatal glutamate and dopamine levels. Local administration of 300 µ M concentration of excitatory receptor agonist kainic acid increased significantly extracellular striatal dopamine in intact freely moving rats. These findings support the hypothesis that glutamate exerts a tonic facilitatory effect on striatal dopamine release. The effect of kainic acid on extracellular striatal glutamate concentration in intact rats was a biphasic increase. The first glutamate increase can be explained by stimulation of presynaptic kainate receptors present on corticostriatal glutamatergic nerve terminals; the second increase is probably the result of a continuous interaction of the different striatal neurotransmitters after disturbance of their balance. Release of dopamine and glutamate was modulated differently in the intact striatum and in the striatum deprived of corticostriatal input. Dopamine release in the denervated striatum after kainate receptor stimulation was significantly lower than in intact striatum, confirming the so-called cooperativity between glutamate and kainic acid. Loss of presynaptic kainate receptors on the glutamatergic nerve terminals after decortication resulted in a loss of effect of kainic acid on glutamate release in denervated striatum. Aspartate showed no significant changes in this study. 相似文献