全文获取类型
收费全文 | 3215篇 |
免费 | 217篇 |
出版年
2023年 | 15篇 |
2022年 | 16篇 |
2021年 | 52篇 |
2020年 | 39篇 |
2019年 | 58篇 |
2018年 | 81篇 |
2017年 | 55篇 |
2016年 | 83篇 |
2015年 | 135篇 |
2014年 | 144篇 |
2013年 | 230篇 |
2012年 | 246篇 |
2011年 | 251篇 |
2010年 | 154篇 |
2009年 | 123篇 |
2008年 | 215篇 |
2007年 | 219篇 |
2006年 | 180篇 |
2005年 | 153篇 |
2004年 | 151篇 |
2003年 | 159篇 |
2002年 | 159篇 |
2001年 | 27篇 |
2000年 | 16篇 |
1999年 | 26篇 |
1998年 | 26篇 |
1997年 | 34篇 |
1996年 | 20篇 |
1995年 | 30篇 |
1994年 | 22篇 |
1993年 | 23篇 |
1992年 | 27篇 |
1991年 | 23篇 |
1990年 | 26篇 |
1989年 | 13篇 |
1988年 | 13篇 |
1987年 | 14篇 |
1986年 | 12篇 |
1985年 | 14篇 |
1984年 | 16篇 |
1983年 | 9篇 |
1982年 | 11篇 |
1981年 | 18篇 |
1980年 | 12篇 |
1979年 | 9篇 |
1978年 | 8篇 |
1977年 | 8篇 |
1976年 | 10篇 |
1975年 | 7篇 |
1971年 | 4篇 |
排序方式: 共有3432条查询结果,搜索用时 15 毫秒
51.
Luigi A. M. Castagnetta Orazia M. Granata Vincenzo Bellavia Rosalba Amodio Eugenia Scaccianoce Monica Notarbartolo Maria R. Follari M. Dora Miceli Giuseppe Carruba 《The Journal of steroid biochemistry and molecular biology》1997,61(3-6):287-292
We investigated conversion rates of androgens to estrogens in cultured, hormone-responsive prostate (LNCaP) and breast (MCF-7) human cancer cells. For this purpose, we adopted an intact cell analysis, whereby cells were incubated for different incubation times in the presence of close-to-physiological (1 nM) or supraphysiological (1 μM) concentrations of labelled androgen precursors, i.e. testosterone (T) and androstenedione (Δ4Ad). The aromatase activity, as measured by estrogen formation, was detected in LNCaP cells (0.5 pmol/ml), even though to a significantly lower extent than in MCF-7 cells (5.4 pmol/ml), using 1 μM T after 72 h incubation. Surprisingly, LNCaP cells displayed a much higher aromatase activity when T was used as a substrate with respect to Δ4Ad. In either cell line, T transformation to Δ4Ad was relatively low, attaining only 2.8% in LNCaP and 7.5% MCF-7 cells. However, T was mostly converted to conjugates (over 95%), glucuronides and some sulphates, in LNCaP cells, whereas it was only partly converted to sulphates (<10%) in MCF-7 cells. Aromatase activity seems to be inconsistent in LNCaP cells, being strongly affected by culture conditions, especially by fetal calf serum (FCS). Further studies should assess the regulation of aromatase expression by serum or growth factors in different human cancer cells, also using anti-aromatase and/or anti-estrogen compounds, in different culture conditions. 相似文献
52.
Adobati Elena; Panza Luigi; Russo Giovanni; Colnaghi Maria I.; Canevari Silvana 《Glycobiology》1997,7(2):173-178
The murine monoclonal antibody (Mab) MBr1, raised against thebreast cancer cell line MCF7, recognizes a saccharidic epitopeoverexpressed on a high percentage of human breast, ovary, andlung carcinomas. This antigen was originally identified on theimmunogen as a globo-series glycosphingolipid with an H-likedeterminant at its terminus (globo-H). We report here the biologicalcharacterization of the entire globo-H hexasaccharide and fivesynthetic oligosaccharides representing fragments of the entirestructure andlor different anomeric configurations. Using competitivebinding assays on live cells, we identified the residues andthe linkages essential for mimicry of the cellular antigensrecognized by Mab MBr1 on the breast carcinoma cell line MCF7and small cell lung cancer cell line POVD. The terminal tetrasaccharidicfragment of globo-H is the oligosaccharide that most resemblesthe MBr1-defined epitope both on glycolipids and on glycoproteins.This information will help in the rational design of a highlyspecific reagent for active specific immunotherapy of carcinomasoverexpressing the MBr1-defined antigen. CaMBr1 immunotherapy monoclonal antibody oligosaccharides tumor-associated antigen 相似文献
53.
Enrico Crivellato Luciana Travan Luigi Candussio Fiora Bartoli Klugmann Giuliana Decorti 《The Histochemical journal》1997,29(3):193-198
The presence of P-glycoprotein has been investigated in rat peritoneal mast cells by means of immunofluorescence and immunogold
electron microscopy, using the specific monoclonal antibody JSB-1. Immunofluorescence studi es showed that the glycoprotein
is primarily concentrated in mast cell granules, and little is localized at the plasma membrane. Electron microscope observations
revealed a marked accumulation of colloidal gold particles at the granule-coating membranes, whereas decoration of the plasma
membrane is much less intense. When mast cells are stimulated to exocytate with compound 48/80, both immunofluorescence and
electron microscopy showed concentration of P-glycoprotein reactivity at the plasma membrane level. Indeed, fusion of the
granule with the plasma membrane allowed transfer of immunoreactive P-glycoprotein material from the granule-coating membrane
to the cell surface membrane. These findings confirmed the presence of P-glycoprotein in mast cells; it is predominantly localized
in the granules and is exposed on the cell surface only after exocytosis, suggesting, therefore, a possible physiological
role for P-glycoprotein in the secretion of certain mediators.
This revised version was published online in November 2006 with corrections to the Cover Date. 相似文献
54.
Characterization of a Small Family (CAIII) of Microsatellite-Containing Sequences with X-Y Homology 总被引:4,自引:0,他引:4
Patrizia Malaspina Bianca Maria Ciminelli Luigi Viggiano Carla Jodice Fulvio Cruciani Piero Santolamazza Daniele Sellitto Rosaria Scozzari Luciano Terrenato Mariano Rocchi Andrea Novelletto 《Journal of molecular evolution》1997,44(6):652-659
Four X-linked loci showing homology with a previously described Y-linked polymorphic locus (DYS413) were identified and characterized.
By fluorescent in situ hybridization (FISH), somatic cell hybrids, and YAC screening, the X-linked members of this small family
of sequences (CAIII) all map in Xp22, while the Y members map in Yq11. These loci contribute to the overall similarity of
the two genomic regions. All of the CAIII loci contain an internal microsatellite of the (CA)n type. The microsatellites display extensive length polymorphism in two of the X-linked members as well as in the Y members.
In addition, common sequence variants are found in the portions flanking the microsatellites in two of the X-linked members.
Our results indicate that, during the evolution of this family, length variation on the Y chromosome was accumulated at a
rate not slower than that on the X chromosome. Finally, these sequences represent a model system with which to analyze human
populations for similar X- and Y-linked polymorphisms.
Received: 29 July 1996 / Accepted: 15 January 1997 相似文献
55.
Characterization of Nine Novel Mutations in the CD40 Ligand Gene in Patients with X-Linked Hyper IgM Syndrome of Various Ancestry 总被引:3,自引:0,他引:3
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Paolo Macchi Anna Villa Dario Strina Maria Grazia Sacco Federica Morali Duilio Brugnoni Silvia Giliani Elide Mantuano Anders Fasth Bengt Andersson Ben J. M. Zegers Giovanni Cavagni Igor Reznick Jacov Levy Israel Zan-Bar Yael Porat Paolo Air Alessandro Plebani Paolo Vezzoni Luigi D. Notarangelo 《American journal of human genetics》1995,56(4):898-906
X-linked immunodeficiency with hyper-IgM (HIGMX-1) is a rare disorder caused by defective expression of the CD40 ligand (CD40L) by activated T lymphocytes, resulting in inefficient T-B cell cooperation and failure of B cells to undergo immunoglobulin isotype switch. In the present work, we describe nine patients of various ancestry who bear different mutations in the X chromosome–specific CD40L gene. Two of the mutations were nonsense mutations, one each resulting in premature stop codons at amino acid residues 39 and 140. Three patients had single point missense mutations, one each at codons 126, 140, and 144. Another patient had a 4-bp genomic deletion in exon 2, resulting in a frameshift and premature termination. Three patients showed insertions, one each of 1, 2, and 4 nt, probably because of polymerase slippage, resulting in frameshift mutation and premature termination. Overall, these observations confirm the heterogeneity of mutations in HIGMX-1. However, the identification of two patients whose mutation involves codon 140 (previously shown to be altered in two other unrelated subjects) suggests that this may be a hotspot of mutation in HIGMX-1. In two additional patients with clinical and immunological features indistinguishable from canonical HIGMX-1, no mutation was detected in the coding sequence, in the 5' flanking region, or in the 3' UTR. 相似文献
56.
Molecular Genetics of Cystinuria: Identification of Four New Mutations and Seven Polymorphisms, and Evidence for Genetic Heterogeneity 总被引:3,自引:2,他引:1
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Paolo Gasparini Maria Julia Calonge Luigi Bisceglia Jesus Purroy Irma Dianzani Angelo Notarangelo Ferran Rousaud Michele Gallucci Xavier Testar Alberto Ponzone Xavier Estivill Antonio Zorzano Manuel Palacin Virginia Nunes Leopoldo Zelante 《American journal of human genetics》1995,57(4):781-788
A cystinuria disease gene (rBAT) has been recently identified, and some mutations causing the disease have been described. The frequency of these mutations has been investigated in a large sample of 51 Italian and Spanish cystinuric patients. In addition, to identify new mutated alleles, genomic DNA has been analyzed by an accurate and sensitive method able to detect nucleotide changes. Because of the lack of information available on the genomic structure of rBAT gene, the study was carried out using the sequence data so far obtained by us. More than 70% of the entire coding sequence and 8 intron-exon boundaries have been analyzed. Four new mutations and seven intragenic polymorphisms have been detected. All mutations so far identified in rBAT belong only to cystinuria type I alleles, accounting for ~44% of all type I cystinuric chromosomes. Mutation M467T is the most common mutated allele in the Italian and Spanish populations. After analysis of 70% of the rBAT coding region, we have detected normal sequences in cystinuria type II and type III chromosomes. The presence of rBAT mutated alleles only in type I chromosomes of homozygous (type I/I) and heterozygous (type I/III) patients provides evidence for genetic heterogeneity where rBAT would be responsible only for type I cystinuria and suggests a complementation mechanism to explain the intermediate type I/type III phenotype. 相似文献
57.
58.
Luigi Valentini Elisabetta Gianazza Pier Giorgio Righetti 《Journal of biochemical and biophysical methods》1980,3(6):323-338
Basic equations have been derived linking the electrophoretic migration in a stationary pH gradient of simple, singly charged cations or anions and of mono- mono- valent ampholytes with the pKs of their ionizable groups. In the case of diprotic ampholytes, an equation and a curve are described calculating a correction factor to be applied to the mobility measurements, accounting for the influence of the opposite charge species on the mobility curve of the ion being measured. This correction factor is a function of ΔpK and increases exponentially with decreasing values of ΔpK. These theoretical considerations have been experimentally verified by running pH-mobility curves of colored compounds, such as methyl red, neutral red and dexorubicin. The pKs thus measured were in excellent agreement with the pKs obtained independently by spectrophotometric titrations. 相似文献
59.
Martijn H. Breuning Ella M. van den Berg-Loonen Luigi F. Bernini Jan B. Bijlsma Erna van Loghem P. Meera Khan Lourens E. Nijenhuis 《Human genetics》1977,37(2):131-139
Summary A detailed marker gene study in a large Dutch kindred segregating for a reciprocal translocation between the chromosomes 6 and 20, t(6;20) (p21;p13), revealed a close linkage between the HLA genes and the breakpoint on the short arm of 6. During this study an apparent peak lod score of 2.9 was obtained at a recombination value of 0.05 for a linkage between HLA and the breakpoint, indicating that the chromosomal region, carrying the HLA genes, is situated near the breakpoint in band 6p21 close to the transition to 6p22. 相似文献
60.
Several N-protected peptide amides, containing two aromatic residues spaced by one glycyl residue, have been enzymatically synthesized starting from P-Ar-OH and H-Gly-Ar-NH2 (P is the protecting group and Ar is the aromatic residue) and using α-chymotrypsin as the catalyst for the coupling step. Reactions have been carried out in water solution, at room temperature, and afford yields ranging between 20 and 75% ca. This coupling reaction occurs in a much more restricted set of conditions than the hydrolysis reaction, e.g., only within a small pH range (ca. 6.5–7.5) and with particular buffering agents. The advantages and limitations of this type of reaction, compared with conventional coupling procedures, are discussed. 相似文献