全文获取类型
收费全文 | 305篇 |
免费 | 30篇 |
出版年
2021年 | 6篇 |
2019年 | 3篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 7篇 |
2015年 | 5篇 |
2014年 | 10篇 |
2013年 | 17篇 |
2012年 | 17篇 |
2011年 | 12篇 |
2010年 | 16篇 |
2009年 | 6篇 |
2008年 | 20篇 |
2007年 | 15篇 |
2006年 | 11篇 |
2005年 | 10篇 |
2004年 | 16篇 |
2003年 | 11篇 |
2002年 | 8篇 |
2001年 | 10篇 |
2000年 | 16篇 |
1999年 | 10篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 9篇 |
1991年 | 6篇 |
1990年 | 7篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1976年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1969年 | 3篇 |
1968年 | 4篇 |
1967年 | 3篇 |
1966年 | 4篇 |
1965年 | 1篇 |
1962年 | 1篇 |
1961年 | 2篇 |
排序方式: 共有335条查询结果,搜索用时 343 毫秒
121.
122.
Ece Gamsiz D Shah LK Devalapally H Amiji MM Carrier RL 《Biotechnology and bioengineering》2008,101(5):1072-1082
Modeling the influence of a technology such as nanoparticle systems on drug delivery is beneficial in rational formulation design. While there are many studies showing drug delivery enhancement by nanoparticles, the literature provides little guidance regarding when nanoparticles are useful for delivery of a given drug. A model was developed predicting intracellular drug concentration in cultured cells dosed with nanoparticles. The model considered drug release from nanoparticles as well as drug and nanoparticle uptake by the cells as the key system processes. Mathematical expressions for these key processes were determined using experiments in which each process occurred in isolation. In these experiments, intracellular delivery of saquinavir, a low solubility drug dosed as a formulation of poly(ethylene oxide)-modified poly(epsilon- caprolactone) (PEO-PCL) nanoparticles, was studied in THP-1 human monocyte/macrophage (Mo/Mac) cells. The model accurately predicted the enhancement in intracellular concentration when drug was administered in nanoparticles compared to aqueous solution. This simple model highlights the importance of relative kinetics of nanoparticle uptake and drug release in determining overall enhancement of intracellular drug concentration when dosing with nanoparticles. 相似文献
123.
Milk thistle (Silybum marianum L.) seed meal is extracted for the flavonolignans, silychristin, silydianin, silybinin A, silybinin B, isosilybinin A and isosilybinin B, which are collectively known as the silymarin complex. To obtain the flavonolignans, the meal is usually treated with successive washes of petroleum ether to remove the lipids, followed by extraction of the flavonolignans with ethanol. This work examines the possible replacement of petroleum ether and ethanol by water or other aqueous solutions in these processes. To replace petroleum ether, pretreatments with 1.2% NaOH (w/w), 1.5% H2SO4 (w/w), 2% NaHCO3 (w/w), 0.14% cellulase and water were investigated. Of these pretreatments, 1.5% H2SO4 and water produced similar flavonolignan yields as petroleum ether. Results established that pretreating the milk thistle seed meal with 1.5% H2SO4 (w/w) at 50 degrees C for 18 h could replace the petroleum ether pretreatment. In addition, it was shown that similar amounts of flavonolignan could be recovered with a 1.5% H2SO4/water (100 degrees C) extraction as with a petroleum ether/ethanol extraction. Although cellulase pretreatment was not examined extensively, significant advances in cellulase effectiveness and cost have occurred in the past few years by companies such as Genencor International and Novozymes. These advances should help to make enzyme use for cellulose conversion, as well as extraction pretreatment, technically and economically feasible. 相似文献
124.
The auxin influx carrier LAX3 promotes lateral root emergence 总被引:1,自引:0,他引:1
Swarup K Benková E Swarup R Casimiro I Péret B Yang Y Parry G Nielsen E De Smet I Vanneste S Levesque MP Carrier D James N Calvo V Ljung K Kramer E Roberts R Graham N Marillonnet S Patel K Jones JD Taylor CG Schachtman DP May S Sandberg G Benfey P Friml J Kerr I Beeckman T Laplaze L Bennett MJ 《Nature cell biology》2008,10(8):946-954
Lateral roots originate deep within the parental root from a small number of founder cells at the periphery of vascular tissues and must emerge through intervening layers of tissues. We describe how the hormone auxin, which originates from the developing lateral root, acts as a local inductive signal which re-programmes adjacent cells. Auxin induces the expression of a previously uncharacterized auxin influx carrier LAX3 in cortical and epidermal cells directly overlaying new primordia. Increased LAX3 activity reinforces the auxin-dependent induction of a selection of cell-wall-remodelling enzymes, which are likely to promote cell separation in advance of developing lateral root primordia. 相似文献
125.
Enhanced Toxic Metal Accumulation in Engineered Bacterial Cells Expressing Arabidopsis thaliana Phytochelatin Synthase 总被引:2,自引:0,他引:2 下载免费PDF全文
Sandrine Sauge-Merle Stphan Cuin Patrick Carrier Catherine Lecomte-Pradines Doan-Trung Luu Gilles Peltier 《Applied microbiology》2003,69(1):490-494
Phytochelatins (PCs) are metal-binding cysteine-rich peptides, enzymatically synthesized in plants and yeasts from glutathione in response to heavy metal stress by PC synthase (EC 2.3.2.15). In an attempt to increase the ability of bacterial cells to accumulate heavy metals, the Arabidopsis thaliana gene encoding PC synthase (AtPCS) was expressed in Escherichia coli. A marked accumulation of PCs was observed in vivo together with a decrease in the glutathione cellular content. When bacterial cells expressing AtPCS were placed in the presence of heavy metals such as cadmium or the metalloid arsenic, cellular metal contents were increased 20- and 50-fold, respectively. We discuss the possibility of using genes of the PC biosynthetic pathway to design bacterial strains or higher plants with increased abilities to accumulate toxic metals, and also arsenic, for use in bioremediation and/or phytoremediation processes. 相似文献
126.
Catherine Vigano Michel Julien Isabelle Carrier Philippe Gros Jean-Marie Ruysschaert 《The Journal of biological chemistry》2002,277(7):5008-5016
The dynamic changes occurring during the catalytic cycle of MDR3 P-glycoprotein (Pgp) and the role of each nucleotide-binding domain (NBD) in the transport process were investigated using attenuated total reflection Fourier transform infrared spectroscopy. For this purpose, wild-type Pgp and two mutations of homologous residues in each NBD were studied. On the one hand, we demonstrate here that, during its catalytic cycle, Pgp does not undergo secondary structure changes, but only modifications in its stability and accessibility to the external environment. On the other hand, amide H/D exchange kinetics demonstrate that homologous mutations in the two NBDs affect, in a different way, the dynamic properties of Pgp and also the dynamic changes occurring during ATP hydrolysis. These observations led to the conclusion that the NBDs have an asymmetric structure and different functions in the catalytic cycle of Pgp. Our data suggest that the release of drug from the membrane into the extracellular environment is due to decreased stability and/or increased accessibility to the external medium of the membrane-embedded drug-binding site(s). NBD1 would play an important role in this first restructuring of the membrane-embedded domains. NBD2 would be directly implicated in the subsequent restructuring of the membrane-embedded binding sites by which they recover their initial stability and accessibility to the membrane. It is proposed that this restructuring step would allow the binding and transport of another molecule of substrate. 相似文献
127.
128.
Identification and characterization of atrial natriuretic factor receptors in the rat retina 总被引:2,自引:0,他引:2
R Fernandez-Durango D Sanchez J Gutkowska F Carrier A Fernandez-Cruz 《Life sciences》1989,44(24):1837-1846
The characteristics of atrial natriuretic factor (ANF) receptors where studied in rat retinal particulate preparations. Specific 125I-ANF binding to retinal particulate preparations was greater than 90% of total binding and saturable at a density (Bmax) of 40 +/- 8 fmol/mg protein with an apparent dissociation constant (Kd) of 6.0 +/- 2.0 pM (n = 3). Apparent equilibrium conditions were established within 30 min. The Kd value of 125I-ANF binding calculated by kinetic analysis was 4.0 pM. The Bmax of 60 +/- 10 fmol/mg protein and the Kd of 5 +/- 2 pM, calculated by competition analysis, were in close agreement with the values obtained from Scatchard plots or kinetic analysis. The 125I-ANF binding to retinal particulate preparations was not inhibited by 1 microM concentration of somatostatin, vasopressin, vasoactive intestinal peptide, adrenocorticotropin, thyrotropin releasing hormone, or leu-enkephalin. The rank order of potency of the unlabelled atrial natriuretic peptides for competing with specific 125I-ANF (101-126) binding sites was rANF (92-126) greater than rANF (101-126) greater than rANF (99-126) greater than rANF (103-126) greater than Tyro-Atriopeptin I greater than hANF (105-126) greater than rANF (1-126). Similar results have been obtained in peripheral tissues and mammalian brain, indicating that central and peripheral ANF-binding sites have somewhat similar structural requirements. Affinity cross-linking of 125I-ANF to retinal particulate preparations resulted in the labelling of two sites of molecular weight 140 and 66 kDa, respectively. This demonstration of specific high-affinity ANF receptors suggests that the peptide may act as a neurotransmitter or neuromodulator in the retina. 相似文献
129.
Replicate cultures of 50000 mouse Leydig cells were used to obtain linear log dose-response curves to LH. This hormone augmented the activity of an endogenous alkaline phosphatase, which was subsequently allowed to act on p-nitrophenyl phosphate, the coloured end-point being measured with a spectrophotometer. The linear portion of the curve extended from 0.2 to 3.2 mi.u. LH/ml. 相似文献
130.
Cut muscle fibers from Rana temporaria (sarcomere length, 3.5–3.9 μm; 14–16°C) were mounted in a double Vaseline-gap chamber and equilibrated with an external solution that contained tetraethyl ammonium– gluconate and an internal solution that contained Cs as the principal cation, 20 mM EGTA, and 0 Ca. Fibers were stimulated with a voltage-clamp pulse protocol that consisted of pulses to −70, −65, −60, −45, and −20 mV, each separated by 400-ms periods at −90 mV. The change in total Ca that entered into the myoplasm (Δ[CaT]) and the Ca content of the SR ([CaSR]) were estimated with the EGTA/phenol red method (Pape, P.C., D.-S. Jong, and W.K. Chandler. 1995. J. Gen. Physiol. 106:259–336). Fibers were stimulated with the pulse protocol, usually every 5 min, so that the resting value of [CaSR] decreased from its initial value of 1,700–2,300 μM to values near or below 100 μM after 18–30 stimulations. Three main findings for the voltage pulses to −70, −65, and −60 mV are: (a) the depletion-corrected rate of Ca release (release permeability) showed little change when [CaSR] decreased from its highest level (>1,700 μM) to ∼1,000 μM; (b) as [CaSR] decreased below 1,000 μM, the release permeability increased to a maximum level when [CaSR] was near 300 μM that was on average about sevenfold larger than the values observed for [CaSR] > 1,000 μM; and (c) as [CaSR] decreased from ∼300 μM to <100 μM, the release permeability decreased, reaching half its maximum value when [CaSR] was ∼110 μM on average. It was concluded that finding b was likely due to a decrease in Ca inactivation, while finding c was likely due to a decrease in Ca-induced Ca release. 相似文献