全文获取类型
收费全文 | 21828篇 |
免费 | 1941篇 |
国内免费 | 234篇 |
出版年
2023年 | 119篇 |
2022年 | 249篇 |
2021年 | 531篇 |
2020年 | 319篇 |
2019年 | 369篇 |
2018年 | 477篇 |
2017年 | 426篇 |
2016年 | 622篇 |
2015年 | 1046篇 |
2014年 | 1064篇 |
2013年 | 1358篇 |
2012年 | 1644篇 |
2011年 | 1560篇 |
2010年 | 1002篇 |
2009年 | 902篇 |
2008年 | 1301篇 |
2007年 | 1165篇 |
2006年 | 1055篇 |
2005年 | 1006篇 |
2004年 | 988篇 |
2003年 | 882篇 |
2002年 | 844篇 |
2001年 | 488篇 |
2000年 | 387篇 |
1999年 | 388篇 |
1998年 | 254篇 |
1997年 | 160篇 |
1996年 | 157篇 |
1995年 | 161篇 |
1994年 | 145篇 |
1993年 | 128篇 |
1992年 | 200篇 |
1991年 | 225篇 |
1990年 | 174篇 |
1989年 | 186篇 |
1988年 | 165篇 |
1987年 | 159篇 |
1986年 | 137篇 |
1985年 | 151篇 |
1984年 | 134篇 |
1983年 | 102篇 |
1982年 | 89篇 |
1981年 | 91篇 |
1980年 | 87篇 |
1979年 | 96篇 |
1978年 | 89篇 |
1977年 | 79篇 |
1975年 | 63篇 |
1974年 | 70篇 |
1973年 | 58篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
111.
H. Nquyen H.H. Le R.Y. Lee M. Staufenbiel J.M. Palacios G. Mengod H. Lübbert 《Neurochemistry international》1991,19(4):433-436
We have previously isolated serotonin 5-HT1C receptor cDNA clones. In contrast to most other receptors coupled to GTP binding proteins, the 5-HT1C receptor gene contains several introns in its coding region. A similar exon-intron distribution is found in the 5-HT2 receptor gene. The presence of large introns tempted us to test whether exchange of exons contributes to serotonin receptor heterogeneity. Therefore, blots with RNAs from different regions of the brain and brain slices were hybridized in situ with probes representing individual exons. We did not find any evidence for the exchange of exons which should result in an unequal distribution of hybridization signals found with the exon-specific probes. With the methodology used we should be able to see differential splicing in the form where individual exons are used alternatively resulting in mRNAs coding for different serotonin receptor types. We would not, however, see if a given exon can be modified by the alternative use of several splice-junctions. 相似文献
112.
113.
Epithelio--mesenchymal interactions are critical for Quox 7 expression and membrane bone differentiation in the neural crest derived mandibular mesenchyme.
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
In higher vertebrates, branchial arch mesenchyme (ectomesenchyme) is derived from the cephalic neural crest. The ectomesenchyme of the mandibular arch yields the Meckel's cartilage and several membrane bones. We previously reported the isolation of a quail homeobox gene, Quox 7. In common with its mouse counterpart Hox 7, Quox 7 is highly expressed in the medioventral part of the mandibular arch and later in the precursor cells of the membrane bones. Since bone differentiation from ectomesenchyme is strictly dependent upon a signal provided by the mandibular epithelium, we decided to see whether the regulation of Quox 7 gene activity might be correlated with epithelio--mesenchymal interactions. Quox 7 expression was studied in E3 mandibular ectomesenchyme cultured in vitro or grafted on the chick chorioallantoic membrane either alone or recombined with the homotopic and heterotopic epithelia. We found that Quox 7 mRNA was undetectable after 48 h in cultures of mesenchyme alone while it remained abundant in non-cartilaginous tissue of the mandibular arch ectomesenchyme recombined with its own epithelium. The signal provided by the mandibular epithelium for Quox 7 expression can also arise from various heterotopic epithelia, e.g. of dorsal or ventral body wall and of limb bud. Thus the effect of the epithelium on Quox 7 expression in mesenchymal cells strictly parallels that on bone formation. These results strongly suggest that the epithelio-mesenchymal interactions have an essential role on the regulation of Quox 7 gene, the product of which seems to be, in turn, necessary for the execution of the skeletal developmental program in the facial area. 相似文献
114.
Solution conformation of an oligonucleotide containing a G.G mismatch determined by nuclear magnetic resonance and molecular mechanics. 总被引:2,自引:1,他引:1
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
J A Cognet J Gabarro-Arpa M Le Bret G A van der Marel J H van Boom G V Fazakerley 《Nucleic acids research》1991,19(24):6771-6779
We have determined by two-dimensional nuclear magnetic resonance studies and molecular mechanics calculations the three dimensional solution structure of the non-selfcomplementary oligonucleotide, d(GAGGAGGCACG). d(CGTGCGTCCTC) in which the central base pair is G.G. This is the first structural determination of a G.G mismatch in a oligonucleotide. Two dimensional nuclear magnetic resonance spectra show that the bases of the mismatched pair are stacked into the helix and that the helix adopts a classical B-DNA form. Spectra of the exchangeable protons show that the two guanosines are base paired via their imino protons. For the non-exchangeable protons and for some of the exchangeable protons nuclear Overhauser enhancement build up curves at short mixing times have been measured. These give 84 proton-proton distances which are sensitive to the helix conformation. One of the guanosines adopts a normal anti conformation while the other is syn or close to syn. All non-terminal sugars are C2' endo. These data sets were incorporated into the refinement of the oligonucleotide structure by molecular mechanics calculations. The G.G mismatch shows a symmetrical base pairing structure. Although the mismatch is very bulky many of its features are close to that of normal B-DNA. The mismatch induces a small lateral shift in the helix axis and the sum of the helical twist above and below the mismatch is close to that of B-DNA. 相似文献
115.
The solution structure of a DNA hairpin containing a loop of three thymidines determined by nuclear magnetic resonance and molecular mechanics. 总被引:7,自引:6,他引:1
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Y Boulard J Gabarro-Arpa J A Cognet M Le Bret A Guy R Toule W Guschlbauer G V Fazakerley 《Nucleic acids research》1991,19(19):5159-5167
We have determined by two-dimensional nuclear magnetic resonance studies and molecular mechanics calculations the three-dimensional solution structure of a 21 residue oligonucleotide capable of forming a hairpin structure with a loop of three thymidine residues. This structure is in equilibrium with a duplex form. At 33 degrees C, low ionic strength and in the presence of MgCl2 the hairpin form dominates in solution. Six Watson-Crick base pairs are formed topped by the loop structure. The residues 1-3 and 18-21 are not complementary and form dangling ends. Distance constraints have been derived from nuclear Overhauser enhancement measurements. These, together with molecular mechanics calculations, have been used to determine the structure. We do not observe stacking of thymidine residues either over the 3' or the 5' end of the stem. 相似文献
116.
Synthesis and physicochemical properties of oligonucleotides built with either alpha-L or beta-L nucleotides units and covalently linked to an acridine derivative. 总被引:3,自引:3,他引:0
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
U Asseline J F Hau S Czernecki T Le Diguarher M C Perlat J M Valery N T Thuong 《Nucleic acids research》1991,19(15):4067-4074
Modified deoxynucleosides 2'-deoxy-beta-L-uridine, beta-L-thymidine, alpha-L-thymidine, 2'-deoxy-beta-L-adenosine and 2'-deoxy-alpha-L-adenosine were synthesized and assembled as homooligomers, respectively: octa-beta-L-deoxyuridylates, octa beta-L and alpha-L-thymidylates and tetra beta-L and alpha-L-deoxyadenylates. These unnatural oligomers were then substituted with an acridine derivative. The binding studies of these modified oligonucleotides with D-ribo- and D-deoxyribopolynucleotides were carried out by absorption spectroscopy. While beta-L-d(Up)8m5Acr, beta-L-(Tp)8m5Acr, alpha-L-(Tp)8m5Acr did not interact with poly(rA) and poly(dA), beta-L-d(Ap)4m5Acr and alpha-L-d(Ap)4m5Acr did form double and triple helices with poly(rU) and poly(dT), respectively. Their stability towards nuclease digestion was studied through comparison with that of octa-beta-D-thymidylate and tetra beta-D-deoxyadenylate covalently linked to an acridine derivative. One endonuclease (nuclease P1 from Penicillium citrinum) and two exonucleases (a 3'-exonuclease from Crotalus durissus venom and a 5'-exonuclease extracted from calf thymus) were employed. beta-L- and alpha-L-oligomers demonstrate a high resistance toward nuclease digestion. 相似文献
117.
Monique Berthelon Catherine Caillaud Françoise Rey Philippe Labrune Dominique Melle Josué Feingold Jean Frézal Marie-Louise Briard Jean-Pierre Farriaux Pierre Guibaud Hubert Journel Bernard Le Marec Nicole Maurin Jean-Louis Nivelon Henri Plauchu Jean-Marie Saudubray Philippe Tron Jean Rey Arnold Münnich Stanislas Lyonnet 《Human genetics》1991,86(4):355-358
Summary A total of 252 chromosomes from 126 patients with phenylalanine hydroxylase (PAH) deficiencies were analyzed for both mutant genotypes and restriction fragment length polymorphism (RFLP) haplotypes at the PAH locus. The mutant genes studied originated either from Western Europe (116 alleles) or from Mediterranean countries (136 alleles). Only 27% of all mutant alleles were found to carry identified mutations, particularly mutations at codon 252 (2.3%), 261 (7.5%), 280 (6.3%), 408 (3.5%) and at the splice donor site of intron 12 (6.3%). The mutant genotypes were associated with RFLP haplotypes 7, 1, 38, 2 and 3 at the PAH locus respectively. Except for the splice mutation of intron 12, these associations were preferential, but not exclusive, since the other four mutations were found on the background of at least two RFLP haplotypes. These results, together with the observation that 85% of PAH deficient patients are heterozygotes for their mutant genotypes, emphasize the great heterogeneity of PAH deficiencies in Mediterranean countries and hamper systematic DNA testing for carrier status in this population. 相似文献
118.
Sandra Wegert John Caprio 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1991,168(2):201-211
1. Receptor sites for different amino acids in the facial taste system of the channel catfish, Ictalurus punctatus, were determined from in vivo electrophysiological cross-adaptation experiments. 2. Relatively independent receptor sites were indicated for L-proline, D-proline, D-arginine, L-histidine and L-lysine, as well as those previously reported for L-alanine, L-arginine and D-alanine. 3. The functional isolation of two nerve twigs that were more responsive to D-alanine than to L-alanine or to other test stimuli provided further evidence for the existence of D-alanine sites that are independent from those to L-alanine. 4. Under all cross-adaptation regimes, the taste responses to the majority of test stimuli were reduced. Various possible mechanisms accounting for this generalized reduction in action potential activity during adaptation are discussed. 相似文献
119.
More than 50% of glutamate decarboxylase (GAD) in brain is present as apoenzyme. Recent work has opened the possibility that apoGAD can be studied in brain by labeling with radioactive cofactor. Such studies would be aided by a compound that inhibits specific binding. One possibility is 4-deoxy-pyridoxine 5-phosphate, a close structural analog of the cofactor pyridoxal 5-phosphate. The effects of deoxypyridoxine-P on the cyclic series of reactions that interconverts apo- and holoGAD was investigated and found to be consistent with simple competitive inhibition of the activation of apoGAD by pyridoxal-P. As expected from the cycle GAD was inactivated when incubated with glutamate and deoxypyridoxine-P even though cofactor was present, but no inactivation was observed with deoxypyridoxine-P in the absence of glutamate. Deoxypyridoxine-P also stabilized apoGAD against heat denaturation. These effects were quantitatively accounted for by a kinetic model of the apo-holoGAD cycle. Deoxypyridoxine-P inhibited the labeling by [32P]pyridoxal-P of GAD isolated from rat brain. Hippocampal extracts were labeled with [32P]pyridoxal-P and analyzed by SDS-polyacrylamide gel electrophoresis. Remarkably few bands were strongly labeled. The major labeled band (at 63 kDa) corresponded to one of the forms of GAD. Other strongly-labeled bands were observed at 65 kDa (corresponding to the higher molecular weight form of GAD) and at 69–72 kDa. Labeling of the 63- and 65-kDa bands was inhibited by deoxypyridoxine-P, but the 69–72 kDa bands were unaffected, suggesting that the latter were non-specifically labeled. The results suggest that the 63-kDa form of GAD makes up the majority of apoGAD in hippocampus.Special issue dedicated to Dr. Eugene Roberts. 相似文献
120.
Use of a simple method for the Epstein-Barr virus transformation of lymphocytes from members of large families of Réunion Island 总被引:2,自引:0,他引:2
A simple method for the preparation of lymphoblastoid cell lines from small amounts (100 microliter) of frozen whole blood is described. A success score greater than 90% was obtained for EBV transformations using blood samples which had been collected several months before the infection. Due to the simplicity of the technique, up to 80 samples could be processed per day. This technique was used to prepared 242 permanent cell lines from 13 large families from Réunion Island showing blood group H deficiency. These cell lines are now available for genetic studies. 相似文献