全文获取类型
收费全文 | 4181篇 |
免费 | 308篇 |
国内免费 | 2篇 |
出版年
2023年 | 13篇 |
2022年 | 36篇 |
2021年 | 60篇 |
2020年 | 47篇 |
2019年 | 52篇 |
2018年 | 53篇 |
2017年 | 73篇 |
2016年 | 93篇 |
2015年 | 191篇 |
2014年 | 185篇 |
2013年 | 261篇 |
2012年 | 338篇 |
2011年 | 357篇 |
2010年 | 231篇 |
2009年 | 203篇 |
2008年 | 302篇 |
2007年 | 246篇 |
2006年 | 253篇 |
2005年 | 235篇 |
2004年 | 232篇 |
2003年 | 239篇 |
2002年 | 206篇 |
2001年 | 53篇 |
2000年 | 37篇 |
1999年 | 53篇 |
1998年 | 53篇 |
1997年 | 36篇 |
1996年 | 46篇 |
1995年 | 42篇 |
1994年 | 32篇 |
1993年 | 20篇 |
1992年 | 39篇 |
1991年 | 13篇 |
1990年 | 22篇 |
1989年 | 18篇 |
1988年 | 16篇 |
1987年 | 13篇 |
1986年 | 7篇 |
1985年 | 14篇 |
1984年 | 14篇 |
1983年 | 13篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 4篇 |
1977年 | 7篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1971年 | 3篇 |
1915年 | 1篇 |
排序方式: 共有4491条查询结果,搜索用时 15 毫秒
1.
Identifying common prognostic factors in genomic cancer studies: A novel index for censored outcomes
Background
With the growing number of public repositories for high-throughput genomic data, it is of great interest to combine the results produced by independent research groups. Such a combination allows the identification of common genomic factors across multiple cancer types and provides new insights into the disease process. In the framework of the proportional hazards model, classical procedures, which consist of ranking genes according to the estimated hazard ratio or the p-value obtained from a test statistic of no association between survival and gene expression level, are not suitable for gene selection across multiple genomic datasets with different sample sizes. We propose a novel index for identifying genes with a common effect across heterogeneous genomic studies designed to remain stable whatever the sample size and which has a straightforward interpretation in terms of the percentage of separability between patients according to their survival times and gene expression measurements. 相似文献2.
3.
Use of ATP bioluminescence measurements for the estimation of biomass during biological humification
Summary The development of the microflora during the humification of grape pulp has been investigated by the determination of ATP using the bioluminescence technique. Several extraction methods were tested including the use of dimethylsulphoxide, trichloroacetic acid, grinding and ultrasonification. Dimethylsulphoxide and ultrasonification for 15 sec appeared to be the most effective. The ATP extract was stabilized when it was mixed with 0.75 mM glycine, 4.4 mM Mg-EDTA, pH 7.5 and frozen. The relative error of the ATP assay by bioluminescence did not exceed 6.5%. This method allowed us to show that at least five distinct reproducible microbial phases exist during grape pulp humification. These results show that the microbial biomass changes noticeably and at distinct times during composting. 相似文献
4.
Expression of alternatively spliced mRNA variants at specific stages of development or in specific cells and tissues contributes to the functional diversity of the human genome. Aberrations in alternative splicing were found as a cause or a contributing factor to the development, progression, or maintenance of numerous diseases. The use of antisense oligonucleotides (ON) to modify aberrant expression patterns of alternatively spliced mRNAs is a novel means of potentially controlling such diseases. Oligonucleotides can be designed to repair genetic mutations, to modify genomic sequences in order to compensate for gene deletions, or to modify RNA processing in order to improve the effects of the underlying gene mutation. Steric block ON approach have proven to be effective in experimental model for various diseases. Here, we describe our experience in investigating two strategies for ON delivery: ON conjugation with basic peptides and lipid-based particulate system (lipoplex). Basic peptides or Cell Penetrating Peptides (CPP) such as the TAT-derived peptide appear to circumvent many problems associated with ON and drug delivery. This strategy may represent the next paradigm in our ability to modulate cell function and offers a unique avenue for the treatment of disease. Lipoplexes result from the intimate interaction of ON with cationic lipids leading to ON carrying particles able to be taken up by cells and to release ON in the cytoplasm. We have used as an experimental model the correction of a splicing alteration of the mutated β-globin intron causing thalassemia. Data on cell penetration and efficacy of correction of specific steric block ON delivered either by basic peptides or lipoplex are described. A comparison of the properties of both delivery systems is made respective to the use of this new class of therapeutic molecules. 相似文献
5.
Horst Grunz Thierry Darribère Jean -Claude Boucaut 《Development genes and evolution》1987,196(4):203-209
Summary Antibodies directed to fibronectin (anti-FN) were injected into the blastocoel of late blastulae of Xenopus laevis. Two animal caps (ectoderm) were isolated, when control embryos reached the early gastrula stage, and were combined with untreated upper blastopore lip in the sandwich method. In two control series fibronectin or Holtfreter solution was injected into the blastocoel. The results of the experiments suggest that neural induction cannot be prevented by binding anti-FN to fibronectin, which covers the blastocoelic side of the ectoderm. The data support the view that extracellular matrix proteins are not themselves responsible for neural induction. However, in comparison with the control series a slight shift of the differentiation pattern in the spinocaudal direction could be observed in the anti-FN series. The possible role of extracellular proteins in the formation of a close juxtaposition of mesodermal and ectodermal target cells as a prerequisite for shortdistance transmission of neural inducers is discussed. 相似文献
6.
7.
Medicago truncatula,a model plant for studying the molecular genetics of theRhizobium-legume symbiosis 总被引:7,自引:0,他引:7
David G. Barker Sylvie Bianchi François Blondon Yvette Dattée Gérard Duc Sadi Essad Pascal Flament Philippe Gallusci Gérard Génier Pierre Guy Xavier Muel Jacques Tourneur Jean Dénarié Thierry Huguet 《Plant Molecular Biology Reporter》1990,8(1):40-49
Medicago truncatula has all the characteristics required for a concerted analysis of nitrogen-fixing symbiosis withRhizobium using the tools of molecular biology, cellular biology and genetics.M. truncatula is a diploid and autogamous plant has a relatively small genome, and preliminary molecular analysis suggests that allelic
heterozygosity is minimal compared with the cross-fertilising tetraploid alfalfa (Medicago sativa). TheM. truncatula cultivar Jemalong is nodulated by theRhizobium meliloti strain 2011, which has already served to define many of the bacterial genes involved in symbiosis with alfalfa. A genotype
of Jemalong has been identified which can be regenerated after transformation byAgrobacterium, thus allowing the analysis ofin-vitro-modified genes in an homologous transgenic system. Finally, by virtue of the diploid, self-fertilising and genetically homogeneous
character ofM. truncatula, it should be relatively straightforward to screen for recessive mutations in symbiotic genes, to carry out genetic analysis,
and to construct an RFLP map for this plant. 相似文献
8.
In this paper, using both immunofluorescence and protein biochemistry techniques, we present definitive evidence that plasma proteins such as albumin are present within normal human epidermis. This result confirms several previous reports supporting the idea that relatively large molecules can diffuse through the epidermal basement membrane into epidermis. Our results bring new insights for discussing how hydrophobic ligands or drugs present in the bloodstream and bound to plasmatic carriers can reach epidermal cells of all layers.Abbreviations CHAPS
3-[3-cholamidopropyl dimethylammonio] propane sulfonate
- kD
kilodaltons
- BSA
bovine serum albumin
- 2ME
2-mercaptoethanol
- DTT
dithiothreitol
- SDS
sodium dodecyl sulfate
- pI
isoelectric point
- Mw
molecular weight
- Tris
Tris-(hydroxymethyl) aminomethane
- 1D
one dimensional
- 2D
two dimensional
- PAGE
poly acrylamide gel electrophoresis
- MEM
Minimal Eagle's Medium 相似文献
9.
Comparative analysis of the intracellular localization of c-Myc, c-Fos, and replicative proteins during cell cycle progression. 下载免费PDF全文
S Vriz J M Lemaitre M Leibovici N Thierry M Méchali 《Molecular and cellular biology》1992,12(8):3548-3555
In eukaryotic cells, nucleus-cytoplasm exchanges play an important role in genomic regulation. We have analyzed the localization of four nuclear antigens in different growth conditions: two replicative proteins, DNA polymerase alpha and proliferating cell nuclear antigen (PCNA), and two oncogenic regulatory proteins, c-Myc and c-Fos. A kinetic study of subcellular localization of these proteins has been done. In cultures in which cells were sparse, these proteins were detected in the nucleus. When proliferation was stopped by the high density of culture cells or by serum starvation, these proteins left the nucleus for the cytoplasm with different kinetics. DNA polymerase alpha is the first protein to leave the nucleus, with the PCNA protein, c-Fos, and c-Myc leaving the nucleus later. In contrast, during serum stimulation c-Fos and c-Myc relocalize into the nucleus before the replicative proteins. We also noticed that in sparse cell cultures, 10% of the cells exhibit a perinuclear staining for the DNA polymerase alpha, PCNA, and c-Myc proteins but not for c-Fos. This peculiar staining was also observed as an initial step to nuclear localization after serum stimulation and in vivo in Xenopus embryos when the G1 phase is reintroduced in the embryonic cell cycle at the mid-blastula stage. We suggest that such staining could reflect specific structures involved in the initiation of the S phase. 相似文献
10.
L. Vitellaro-Zuccarello R. Garbelli V. Dal Pozzo Rossi 《Cell and tissue research》1992,268(3):505-511
Summary The distribution of collagen types I, III, IV, and of fibronectin has been studied in the human dermis by light and electron-microscopic immunocytochemistry, using affinity purified primary antibodies and tetramethylrhodamine isothiocyanate-conjugated secondary antibodies. Type I collagen was present in all collagen fibers of both papillary and reticular dermis, but collagen fibrils, which could be resolved as discrete entities, were labeled with different intensity. Type III collagen codistributed with type I in the collagen fibers, besides being concentrated around blood vessels and skin appendages. Coexistence of type I and type III collagens in the collagen fibrils of the whole dermis was confirmed by ultrastructural double-labelling experiments using colloidal immunogold as a probe. Type IV collagen was detected in all basement membranes. Fibronectin was distributed in patches among collagen fibers and was associated with all basement membranes, while a weaker positive reaction was observed in collagen fibers. Ageing caused the thinning of collagen fibers, chiefly in the recticular dermis. The labeling pattern of both type I and III collagens did not change in skin samples from patients of up to 79 years of age, but immunoreactivity for type III collagen increased in comparison to younger skins. A loss of fibronectin, likely related to the decreased morphogenetic activity of tissues, was observed with age. 相似文献