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991.
Joanna Skommer Tom Brittain Subhadip Raychaudhuri 《Apoptosis : an international journal on programmed cell death》2010,15(10):1223-1233
BH3 mimetics have been proposed as new anticancer therapeutics. They target anti-apoptotic Bcl-2 proteins, up-regulation of
which has been implicated in the resistance of many cancer cells, particularly leukemia and lymphoma cells, to apoptosis.
Using probabilistic computational modeling of the mitochondrial pathway of apoptosis, verified by single-cell experimental
observations, we develop a model of Bcl-2 inhibition of apoptosis. Our results clarify how Bcl-2 imparts its anti-apoptotic
role by increasing the time-to-death and cell-to-cell variability. We also show that although the commitment to death is highly
impacted by differences in protein levels at the time of stimulation, inherent stochastic fluctuations in apoptotic signaling
are sufficient to induce cell-to-cell variability and to allow single cells to escape death. This study suggests that intrinsic
cell-to-cell stochastic variability in apoptotic signaling is sufficient to cause fractional killing of cancer cells after
exposure to BH3 mimetics. This is an unanticipated facet of cancer chemoresistance. 相似文献
992.
Jennifer L. Belsky Alyssa J. Ashley Premal A. Bhatt Karen V. Gilbert Heather R. Joyce Chunhua Pan Horacio Pappa Samir Z. Wahab 《AAPS PharmSciTech》2010,11(2):994-1004
The water-insoluble procedures in US Pharmacopeia (USP) General Chapter Residual Solvents <467>, which are based on European Pharmacopoeia procedures, were optimized and modified before their inclusion in the chapter to improve their scope, performance, and ruggedness.
The optimized procedures use a static headspace introduction system with a gas chromatograph equipped with a flame ionization
detector. This article describes some of the key changes made to the USP published procedures, including use of dimethyl sulfoxide
(DMSO) or dimethylformamide (DMF) as the solvent, addition of 5 mL of water and 1 mL of sample (dissolved in DMSO or DMF)
to the headspace vial, use of a 3:1 GC split ratio, and use of new matrix-matched system suitability solutions. These procedures
were verified with two different active pharmaceutical ingredients—hydroxyzine pamoate and prednisone. In the investigation,
the more polar material (hydroxyzine pamoate) showed greater recoveries for the optimized procedures when prepared in DMSO.
The less polar material (prednisone) typically had greater recoveries in DMF for the optimized procedures. During experimentation,
insights into sample preparation, additional types of headspace instrumentation, solvent purity, and other parameters were
also gained. 相似文献
993.
Md. Abdullahil Baque Eun-Joo Hahn Kee-Yoeup Paek 《In vitro cellular & developmental biology. Plant》2010,46(1):71-80
An efficient protocol for adventitious root induction from leaf explants of Morinda citrifolia treated with different concentrations of indole-3-butyric acid (IBA) and α-naphthaleneacetic acid (NAA) was established in
relation to physiological process changes during adventitious root induction under different light sources (fluorescent, red,
blue, red + blue, and far-red). Among the different concentrations of IBA and NAA, 1.0 mg l−1 IBA was proven as the best auxin source for adventitious root induction under fluorescent light. Higher concentrations of
IBA and NAA trigger callus formation in both light and dark conditions. Maximum numbers of adventitious roots were induced
under red light (26) followed by blue light (22) and the lowest under far-red light (6). In contrast, numerous callus formations
were induced by red + blue followed by red and blue, while the highest root length (1.66 cm) with negligible callusing was
observed under fluorescent light. Catalase and guaicacol peroxidase activities were highest under red light followed by fluorescent
light and the lowest under red + blue light, but superoxide dismutase activity was not significantly influenced by different
light sources. Ascorbate peroxidase played an important role in detoxification of the harmful effects of hydrogen peroxide
(H2O2). Under fluorescent light, significantly lower accumulation of H2O2 was observed. Accumulation of H2O2 in the induced root under different light showed a positive correlation with peroxidation of lipids and was observed higher
under far-red followed by red + blue and blue light. 相似文献
994.
Dietrich Trümbach Cornelia Graf Benno Pütz Claudia Kühne Marcus Panhuysen Peter Weber Florian Holsboer Wolfgang Wurst Gerhard Welzl Jan M Deussing 《BMC systems biology》2010,4(1):159
Background
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of complex and multifactorial psychiatric diseases such as anxiety and mood disorders. About 50-60% of patients with major depression show HPA axis dysfunction, i.e. hyperactivity and impaired negative feedback regulation. The neuropeptide corticotropin-releasing hormone (CRH) and its receptor type 1 (CRHR1) are key regulators of this neuroendocrine stress axis. Therefore, we analyzed CRH/CRHR1-dependent gene expression data obtained from the pituitary corticotrope cell line AtT-20, a well-established in vitro model for CRHR1-mediated signal transduction. To extract significantly regulated genes from a genome-wide microarray data set and to deduce underlying CRHR1-dependent signaling networks, we combined supervised and unsupervised algorithms. 相似文献995.
Triploid Fritillaria camschatcensis (L.) Ker-Gawler (2n = 3x = 36) is a wild species growing in the low-lying areas of Hokkaido Island, Japan, including the Sapporo campus of Hokkaido
University. Many F. camschatcensis plants grew on the campus about a century ago, but we seldom find the plants nowadays and so a project to restore this species
is being planned. Because preservation of genetic diversity and composition in populations has become a major target of conservation,
this study compared variation in the F. camschatcensis population on the Sapporo campus with that in two other populations in Hokkaido. Phenetic variation assessed by 57 randomly
amplified polymorphic DNA markers showed that the three populations were significantly distinct from each other; analysis
of molecular variance showed 64.3% of variation (P < 0.001) existed among the three populations. Comparison of phenetic diversity on the Sapporo campus population with that
in the two other populations showed that the Sapporo campus population contained large genetic variation despite reduced plant
numbers. These results indicate that multiplying F. camschatcensis individuals on the Sapporo campus is adequate to restore the Sapporo campus population because this population contains enough
genetic diversity, and that transplanting from other populations should be avoided so as not to introduce different genotypes
into the campus. These results will be used to design the restoration strategy. 相似文献
996.
Michel Batista Fabricio K Marchini Paola AF Celedon Stenio P Fragoso Christian M Probst Henrique Preti Luiz S Ozaki Gregory A Buck Samuel Goldenberg Marco A Krieger 《BMC microbiology》2010,10(1):259
Background
The three trypanosomatids pathogenic to men, Trypanosoma cruzi, Trypanosoma brucei and Leishmania major, are etiological agents of Chagas disease, African sleeping sickness and cutaneous leishmaniasis, respectively. The complete sequencing of these trypanosomatid genomes represented a breakthrough in the understanding of these organisms. Genome sequencing is a step towards solving the parasite biology puzzle, as there are a high percentage of genes encoding proteins without functional annotation. Also, technical limitations in protein expression in heterologous systems reinforce the evident need for the development of a high-throughput reverse genetics platform. Ideally, such platform would lead to efficient cloning and compatibility with various approaches. Thus, we aimed to construct a highly efficient cloning platform compatible with plasmid vectors that are suitable for various approaches. 相似文献997.
Vaishali A. Kilor Nidhi P. Sapkal Jasmine G. Awari Bharti D. Shewale 《AAPS PharmSciTech》2010,11(1):336-343
In the present study, an attempt was made to prepare immediate-release enteric-coated pellets of aceclofenac, a poorly soluble
nonsteroidal anti-inflammatory drug that has a gastrointestinal intolerance as its serious side effect. Formulation of enteric-coated
pellets with improved solubility of aceclofenac could address both of these problems. To achieve these goals, pellets were
prepared by extrusion–spheronization method using pelletizing agents that can contribute to the faster disintegration and
thereby improve the solubility of the drug. Different disintegrants like β-cyclodextrin, kollidon CL, Ac-Di-Sol, and sodium
starch glycolate were tried in order to further improve disintegration time. The pellets were characterized for drug content,
particle size distribution, flow properties, infrared spectroscopy, surface morphology, disintegration rate, and dissolution
profile. The formulations, which showed best disintegration and dissolution profiles, were coated with Eudragit L100-55, an
enteric-coated polymer which does not dissolve at gastric pH but dissolves at intestinal pH, releasing the drug immediately
in the dissolution medium. The optimized enteric-coated formulation containing 20% κ-carrageenan, lactose, and sodium starch
glycolate as a disintegrant did inhibit the release of the drug for 2 h in 0.1 N HCl, whereas 87% of the drug was released
within 45 min. The improvement was substantial when it was compared with solubility of pure drug under the same conditions.
Thus, dissolution profiles suggested that combination of κ-carrageenan and sodium starch glycolate resulted into fast-disintegrating,
immediate-release pellets, overcoming the bioavailability problem of the poorly soluble drug, aceclofenac, and enteric coating
of these pellets avoids the exposure of aceclofenac to ulcer-prone areas of the gastrointestinal tract. 相似文献
998.
Ko Woon Lee Kyoungseon Min Kyungmoon Park Young Je Yoo 《Biotechnology and Bioprocess Engineering》2010,15(4):603-607
Biodiesel has been greatly interested as an alternative fuel and is produced by a transesterification reaction of oil with
alcohol. Recently, microbial lipases have been used for biodiesel production. Among the microbial lipase, immobilized Candida antartica lipase B (CALB) is the most widely used. However, CALB is unstable and shows low catalytic efficiency in the reaction media
because the reaction media contains a high concentration of methanol and the lipase is also inhibited by the by-product glycerol.
In this study, to overcome these limitations, we developed an amphiphilic matrix to immobilize CALB. The immobilized lipase
in an amphiphilic matrix with 80% ethyltrimethoxysilane (ETMS) in tetramethoxysilane (TMOS) and pretreated with oil showed
the highest specific activity and biodiesel conversion ratio; about 90% biodiesel conversion in 24 h at an initial molar ratio
of 1: 1 (oil: methanol) with stepwise methanol feeding in order to adjust the net molar ratio to be 1: 3. 相似文献
999.
Previous microdialysis studies performed in rats have revealed a decrease of striatal dopamine and glutamate induced by nitrogen
narcosis. We sought to establish the hypothetical role of the glutamatergic corticostriatal pathway because of the glutamate
deficiency which occurs in the basal ganglia in this hyperbaric syndrome. Retrodialysis with 1 mM of Saclofen and 100 mM of
KCl in the prefrontal cortex under normobaric conditions led to an increase in striatal levels of glutamate by 95.2% and no
changes in dopamine levels. Under 3 MPa of nitrogen and with the infusion, the rate of striatal glutamate decreased by 51.3%,
to a greater extent than under pressurised nitrogen alone (−23.8%). The rate of dopamine decreased, which also occurred under
pressurised nitrogen (−36.9 and −31.4%, respectively). In conclusion, the function of the corticostriatal pathway is affected
by nitrogen under pressure. This suggests that the nitrogen-induced break point seems to be located at the glutamatergic striatopetal
neurons. 相似文献
1000.
Hélia Guerra Cardoso Maria Catarina Campos Maria Salomé Pais Augusto Peixe 《In vitro cellular & developmental biology. Plant》2010,46(6):499-508
Somatic embryogenesis induction from in vitro cultured stamens and carpels is highly dependent on explants’ inoculation at specific developmental stages. To establish
good correlations between measurable morphometric parameters of flowers or flower buds and developmental stages of micro-
and macrosporogenesis, this procedure is the easiest way to simplify the in vitro culture procedures. These correlations were established here for the most important Iberian grapevine cultivar, the “Aragonez”,
named “Tempranillo” in Spain and “Tinta Roriz” in the north of Portugal, and were based in floral buds and anther measurements.
The anther length, with a correlation coefficient of 0.90, proved to be the best morphometric parameter to follow microsporogenesis
evolution. A correlation between micro- and macrosporogenesis evolutionary stages was also positively established, allowing
the use of morphometric parameters for tracking ovule evolution as well. Carpels in several evolutionary stages were in vitro cultured to evaluate the aging effect on the capacity for somatic embryogenesis induction. Explants inoculated in the earliest
stages of macrosporogenesis presented the best results. Media culture formulations were also tested for ovary culture, with
the best results being achieved with a 5:1 auxin/cytokinin ratio. 相似文献