全文获取类型
收费全文 | 811篇 |
免费 | 36篇 |
国内免费 | 20篇 |
出版年
2024年 | 1篇 |
2023年 | 12篇 |
2022年 | 10篇 |
2021年 | 20篇 |
2020年 | 25篇 |
2019年 | 29篇 |
2018年 | 36篇 |
2017年 | 19篇 |
2016年 | 16篇 |
2015年 | 19篇 |
2014年 | 58篇 |
2013年 | 67篇 |
2012年 | 45篇 |
2011年 | 55篇 |
2010年 | 43篇 |
2009年 | 31篇 |
2008年 | 43篇 |
2007年 | 42篇 |
2006年 | 49篇 |
2005年 | 29篇 |
2004年 | 33篇 |
2003年 | 26篇 |
2002年 | 29篇 |
2001年 | 23篇 |
2000年 | 13篇 |
1999年 | 13篇 |
1998年 | 12篇 |
1997年 | 6篇 |
1996年 | 6篇 |
1995年 | 12篇 |
1994年 | 7篇 |
1993年 | 5篇 |
1992年 | 3篇 |
1991年 | 7篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有867条查询结果,搜索用时 39 毫秒
1.
2.
A continuous-culture approach to the question of inorganic carbon concentration by Synechococcus species 总被引:1,自引:0,他引:1
Abstract Chemostat cultures of Synechococcus PCC7942 were established in steady state over ten generations with inorganic carbon-limiting biomass production. The bicarbonate-concentration process was not significantly induced; RuBisCo activity was increased six-fold with decreasing dissolved inorganic carbon concentration and the presence of the 42-kDa cytoplasmic membrane polypeptide was observed but not implicated in the process. 相似文献
3.
Else K. Hoffmann Ian H. Lambert Lars Ole Simonsen 《The Journal of membrane biology》1986,91(3):227-244
Summary The net loss of KCl observed in Ehrlich ascites cells during regulatory volume decrease (RVD) following hypotonic exposure involves activation of separate conductive K+ and Cl– transport pathways. RVD is accelerated when a parallel K+ transport pathway is provided by addition of gramicidin, indicating that the K+ conductance is rate limiting. Addition of ionophore A23187 plus Ca2+ also activates separate K+ and Cl– transport pathways, resulting in a hyperpolarization of the cell membrane. A calculation shows that the K+ and Cl– conductance is increased 14-and 10-fold, respectively. Gramicidin fails to accelerate the A23187-induced cell shrinkage, indicating that the Cl– conductance is rate limiting. An A23187-induced activation of42K and36Cl tracer fluxes is directly demonstrated. RVD and the A23187-induced cell shrinkage both are: (i) inhibited by quinine which blocks the Ca2+-activated K+ channel. (ii) unaffected by substitution of NO
3
–
or SCN– for Cl–, and (iii) inhibited by the anti-calmodulin drug pimozide. When the K+ channel is blocked by quinine but bypassed by addition of gramicidin, the rate of cell shrinkage can be used to monitor the Cl– conductance. The Cl– conductance is increased about 60-fold during RVD. The volume-induced activation of the Cl– transport pathway is transient, with inactivation within about 10 min. The activation induced by ionophore A23187 in Ca2+-free media (probably by release of Ca2+ from internal stores) is also transient, whereas the activation is persistent in Ca2+-containing media. In the latter case, addition of excess EGTA is followed by inactivation of the Cl– transport pathway. These findings suggest that a transient increase in free cytosolic Ca2+ may account for the transient activation of the Cl– transport pathway. The activated anion transport pathway is unselective, carrying both Cl–, Br–, NO
3
–
, and SCN–. The anti-calmodulin drug pimozide blocks the volume- or A23187-induced Cl– transport pathway and also blocks the activation of the K+ transport pathway. This is demonstrated directly by42K flux experiments and indirectly in media where the dominating anion (SCN–) has a high ground permeability. A comparison of the A23187-induced K+ conductance estimated from42K flux measurements at high external K+, and from net K– flux measurements suggests single-file behavior of the Ca2+-activated K+ channel. The number of Ca2+-activated K+ channels is estimated at about 100 per cell. 相似文献
4.
In a controlled animal experiment the effects of dietary subacute Zn deficiency on growth, Zn concentration, and tissue 42-K
distribution were studied. Growth retardation caused lower body weight because both skeletal and heart muscle showed a reduction
in cell mass. Zn concentrations were reduced in most tissues, however, they remained unaltered in heart muscle. 42-K activity
increased in skeletal muscle and pancreas. We hypothesize the latter reflects the organs rate of metabolism, inducing the
exocrine pancreas to increase Zn absorption; in skeletal muscle it may induce also alterations in cell potentiation, causing
restless behavior. As suggested by the calculated specific K activity (Bq/mol), the K uptake was highest in liver and bone,
high in pancreas and skeletal muscle and low in heart muscle. The latter suggests K retention in heart muscle. Specific activity
in plasma and jejunum remained unaltered: K status and absorption seem unaffected. Zn deficiency causes different 42-K activities
in the various tissues, that respond by alterations in K metabolism without the induction of K deficiency. 相似文献
5.
Seiji Ichida Tetsuyuki Wada Masahiro Sekiguchi Hiroyuki Kishino Yuko Okazaki Takafumi Akimoto 《Neurochemical research》1993,18(11):1137-1144
Characteristics of specific125I-omega-conotoxin (-CgTX) binding were systematically investigated in crude membranes from rat whole brain. Kd and Bmax Values for the binding were 49.7 pM and 181.5 fmol/mg of protein, respectively. The effects of various types of Ca channel antagonists on the binding were investigated. Dynorphin A (1–13), in particular, specifically inhibited125I--CgTX binding, but not that of [3H](+)PN200-110. Spider venom fromPlectreurys tristes did not specifically inhibit specific binding of125I--CgTX, because the venom also inhibited the binding of [3H](+)PN200-110 to a similar degree. The amount of specific binding of125I--CgTX was less in the cerebellum than that in any other area of whole brain. The cross-linker disuccinimidyl suberate did not label with125I--CgTX and its binding sites in rat whole brain, although it did in chick whole brain, which was used as a positive control. These findings suggested that dynorphine A (1–13) was a selective blocker of -CgTX-sensitive Ca channels in crude membranes from rat whole brain and that -CgTX-sensitive Ca channels were mainly present a rat brain except cerebellum. 相似文献
6.
7.
C-H. Shu W. K. Yang T-S. Huang 《Apoptosis : an international journal on programmed cell death》1996,1(2):141-146
Paclitaxel is a potential cancer chemotherapeutic agent for ovary, breast, and head and neck cancers; its effects on nasopharyngeal
carcinoma (NPC) have not been reported previously. This study investigated the cytotoxic mechanism of paclitaxel in two NPC
cell lines, NPC-TW01 and NPC-TW04. NPC cells treated with pacli-taxel showed convoluted nuclei, condensed chromatin and decreased
cellular and nuclear volume, and also exhibited genomic DNA degradation into multiple oligonucleosomal fragments, suggesting
that pacli-taxel induced apoptosis in these cells. The effects of paclitaxel on apoptosis-related proteins including Bcl-2,
Bax and CDC 2 were also detected. Although the levels of Bcl-2 and Bax were not changed in NPC cells following treatment with
5 nM-1 μM of paclitaxel, phosphorylation of Bcl-2 was significantly observed in the cells treated with 1 μM of paclitaxel
for 12 hours. In addition, cyclin B1-associated CDC 2 kinase was highly activated in the NPC cells exposed to paclitaxel even
at low (5 nM) concentration, and this result is associated with the finding that low concentration of paclitaxel is able to
induce apoptosis in NPC cells. 相似文献
8.
Carlo V. Bruschi John N. McMillan Maristella Coglievina Michael S. Esposito 《Molecular & general genetics : MGG》1995,249(1):8-18
When diploid cells of Saccharomyces cerevisiae homozygous for the temperature-sensitive cell division cycle mutation cdc6-1 are grown at a semipermissive temperature they exhibit elevated genomic instability, as indicated by enhanced mitotic gene conversion, mitotic intergenic recombination, chromosomal loss, chromosomal gain, and chromosomal rearrangements. Employing quantitative Southern analysis of chromosomes separated by transverse alternating field gel electrophoresis (TAFE), we have demonstrated that 2N-1 cells monosomic for chromosome VII, owing to the cdc6-1 defect, show slow growth and subsequently yield 2N variants that grow at a normal rate in association with restitution of disomy for chromosome VII. Analysis of TAFE gels also demonstrates that cdc6-1/cdc6-1 diploids give rise to aberrant chromosomes of novel lengths. We propose an explanation for the genomic instability induced by the cdc6-1 mutation, which suggests that hyper-recombination, chromosomal loss, chromosomal gain and chromosomal rearrangements reflect aberrant mitotic division by cdc6-1/cdc6-1 cells containing chromosomes that have not replicated fully. 相似文献
9.
Putative morphogen, DIF, of Dictyostelium discoideum induces apoptosis in rat pancreatic AR42J cells
Yuzuru Kubohara Chiharu Kimura Kazuhiko Tatemoto 《Development, growth & differentiation》1995,37(6):711-716
We have recently shown that differentiation-inducing factor-1 (DIF-1) of Dictyostelium discoideum is capable of raising intracellular calcium concentration ([Ca2+ ]i ) and suppressing cell proliferation of rat pancreatic AR42J cells in a dose-dependent manner, and that DIF-1 at a concentration of 40 μmol/L is toxic to the cells. In this study, we have further characterized the cytotoxic effect of DIF-1 on AR42J cells and have analyzed the effect of DIF-1 on [Ca2+ ]i . In the presence of 40 μmol/L DIF-1, cells began to bleb after approximately 6 h, and most had died within 48 h. Biochemical analysis revealed that DNA fragmentation was accompanied by cell death. Monitoring the changes in [Ca2+ ]i induced by DIF-1, it was found that cells were able to adapt to stimulation with DIF-1 so that they did not respond to subsequent stimulation by DIF-1. These results indicate that DIF-1 induced apoptosis in AR42J cells probably via a cell signaling system. 相似文献
10.
Previously, tau protein kinase I/glycogen synthase kinase-3/kinase FA(TPKI/GSK-3/FA) was identified as a brain microtubule-associated tau kinase possibly involved in the Alzheimer disease-like phosphorylation of tau. In this report, we find that the TPKI/GSK-3/FA can be stimulated to phosphorylate brain tau up to 8.5 mol of phosphates per mol of protein by heparin, a polyanion compound. Tryptic digestion of32P-labeled tau followed by high-performance liquid chromatography and high-voltage electrophoresis/thin-layer chromatography reveals 12 phosphopeptides. Phosphoamino acid analysis together with sequential manual Edman degradation and peptide sequence analysis further reveals that TPKI/GSK-3//FA after heparin potentiation phosphorylates tau on sites of Ser199, Thr231, Ser235, Ser262, Ser396, and Ser400, which are potential sites abnormally phosphorylated in Alzheimer tau and potent sites responsible for reducing microtubule binding possibly involved in neuronal degeneration. The results provide initial evidence that TPKI/GSK-3/FA after heparin potentiation may represent one of the most potent systems possibly involved in the abnormal phosphorylation of PHF-tau and neuronal degeneration in Alzheimer disease brains.Abbreviations FA
the activating factor of type 1 protein phosphatase
- GSK-3
glycogen synthase kinase-3
- TPKI
tau protein kinase I
- SDS-PAGE
sodium dodecylsulfate-polyacrylamide gel electrophoresis
- PHF
paired helical filaments
- HPLC
high-performance liquid chromatography 相似文献