全文获取类型
收费全文 | 814篇 |
免费 | 32篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 16篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 3篇 |
2017年 | 8篇 |
2016年 | 13篇 |
2015年 | 35篇 |
2014年 | 27篇 |
2013年 | 60篇 |
2012年 | 66篇 |
2011年 | 64篇 |
2010年 | 29篇 |
2009年 | 34篇 |
2008年 | 59篇 |
2007年 | 51篇 |
2006年 | 42篇 |
2005年 | 39篇 |
2004年 | 47篇 |
2003年 | 38篇 |
2002年 | 31篇 |
2001年 | 10篇 |
2000年 | 8篇 |
1999年 | 14篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 12篇 |
1995年 | 5篇 |
1994年 | 7篇 |
1993年 | 10篇 |
1992年 | 8篇 |
1991年 | 9篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1984年 | 9篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 4篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1973年 | 1篇 |
排序方式: 共有846条查询结果,搜索用时 109 毫秒
1.
2.
Mark Andrews Alan Brown Jean-Yves Chiva David Fradet David Gordon Mark Lansdell Malcolm MacKenny 《Bioorganic & medicinal chemistry letters》2009,19(8):2329-2332
The reported selective serotonin Re-uptake Inhibitor Litoxetine was used as the starting point in the design of a range of potential SSRIs with high ease of synthetic accessibility. Preparation and subsequent optimization yielded a range of potent and highly selective SSRIs. 相似文献
3.
4.
Raymond Hellio Dr. Claude Fréhel Jean-Yves Rauzier Nalin Rastogi 《Current microbiology》1988,17(4):235-242
Cytochemical characterization of mycobacterial surfaces was carried out on virulent (H37Rv) and avirulent (H37Ra) strains ofMycobacterium tuberculosis. The results were quantified and compared with those obtained with three colony types of the opportunistic pathogenMycobacterium avium. Mycobacterium aurum, a rapidly growing, nonpathogenic species, served as a model for the cytochemical methods. Concanavalin A (ConA) reacted with -d-mannose and -d-glucose residues, whereas negative charged residues were detected with either the ionized ferritin (CF) or the colloidal ferric hydroxide (CIH) method. Strongly acidic sulfate groups were detected by their selective blockage with alcian blue (AB) at pH 1 prior to the CIH labeling at pH 1.8. Weakly acidic groups were demonstrated by AB blockage at pH 2.5 prior to staining with CF stain. Except forM. aurum, all other strains showed a marked heterogeneity in regard to the abundance of their surface labeling. Accessible sulfate groups were present on the cell surface of the virulent H37Rv strain ofM. tuberculosis, but not on the avirulent strain H37Ra. Distribution of ConA receptors, on the other hand, was unrelated to the virulence or pathogenicity of the bacterial strain. 相似文献
5.
Variants of the anti-Müllerian hormone gene in a compound heterozygote with the persistent Müllerian duct syndrome and his family 总被引:25,自引:0,他引:25
Danièle Carré-Eusèbe Sandrine Imbeaud Madeleine Harbison Maria I. New Nathalie Josso Jean-Yves Picard 《Human genetics》1992,89(4):389-394
Summary The human genome contains a large number of interspersed simple repeat sequences that are variable in length and can therefore serve as highly informative, polymorphic markers. Typing procedures include conventional multilocus and single locus probing, and polymerase chain reaction aided analysis. We have identified simple sequences in a cosmid clone stemming from the human Y chromosome and consisting of (gata)n repeats. We have compared these with two equivalent simple repeat loci from chromosome 12. After amplifying the tandemly repeated motifs, we detected between four and eight different alleles at each of the three loci. Codominant inheritance of the alleles was established in family studies and the informativity of the simple repeat loci was determined by typing unrelated individuals. The polymorphisms are suitable for application in linkage studies, practical forensic case work, deficiency cases in paternity determination, and for studying ethnological questions. The mutational mechanisms that bring about changes in simple repeats located both on the autosomes and on the sex chromosomes, are discussed.Professor Dr. Otto Prokop (Humboldt-Universität Berlin) on the occasion of his 70th birthday 相似文献
6.
Paul Salers L'Houcine Ouafik Pierre Giraud Anne Dutour Jean-Yves Maltese Charles Oliver 《Molecular and cellular biochemistry》1991,106(1):15-24
Thyrotropin-R eleasing hormone (TRH)-degrading pyroglutamyl peptidase I(PGP I) and prolyl endopeptidase (PE) activities have been demonstrated in rat insulinoma RINm 5F cell line. These two enzymes catalyze the conversion of TRH to Histydyl-Proline-Diketopiperazine and to acid TRH respectively.After cell fractionation, we found all the PGP I and PE activities in the cytosolic fraction. The membranebound PGP II activity is not detectable in the RINm 5F cells. Further investigations on these two cytosolic enzymes show that pyroglutamyl- and proline-containing peptides are inhibitors of each TRH-degrading enzyme.Gelfiltration chromatography on Sephadex G100 shows that PGP I and PE activity have an apparent molecular mass of about 18 kDa and 57 kDa, respectively. Kinetic analysis with TRH as substrate, gives a Km of 44 µM and 235 µM, and a Vmax of 1.49 and 8.80 pmoUmin/µg protein for PGP I and PE, respectively. Immunoreactive TRH, His-Pro-Diketopiperazine and acid TRH levels in the cell line extracts are 2.2 ± 0.9, 22.5 ± 11.1 and 28.7 ± 14.6pg/106 cells, respectively. When cells have been incubated for 2 to 72 hours with a P. E. inhibitor (Z-Gly-Pro-CHN2) at 5 × 10–7M, both cell PGP I and PE activities are inhibited. No change in the cellular content of immunoreactive TRH, His-Pro-Diketopiperazine and acid TRH have been observed in treated cells.These data suggest that TRH is not degraded by cytosolic, unspecific PGP I and PE enzymes in RINm 5F. The finding that these cells contain 10 and 13 times more His-Pro-Diketopiperazine and acid TRH than TRH may be an indirect evidence for the existence of another precursor than TRH for these two peptides or of the possibility that TRH can be degraded by other peptidases.Abbreviations TRH
Thyrotropin-Releasing Hormone or Thyroliberin
- His-Pro-DKP
Histidyl-ProlineDiketopiperazine
- TRH-OH
acid TRH or deamidated TRH
- LH-RH
Luteinizing Hormone-Releasing Hormone
- Z-Gly-Pro-CHN2
N-benzyloxycarboxyl-Gly-Pro-diazomethylketone
- PGP
Pyroglutamyl Peptidase, PGP I (EC 3.4.19.3) and PGP II (EC 3.4.19.-)
- PE
Prolyl Endopeptidase or post-proline cleaving enzyme (EC 3.4.21.26) 相似文献
7.
Elisabetta Zappone Isabelle Dugast Panos Papadopoulos Kelly Theriault Veronique David Jean-Yves LeGall Kim Summers Lawrie Powell Jim Drysdale 《Human genetics》1991,86(6):557-561
Summary This paper addresses the question of whether abnormalities in ferritin expression in the iron storage disease hemochromatosis (HC) involve major deletions or alterations in regions containing the two ferritin H genes that lie near the disease locus on chromosome 6p. We present evidence from analyses of Southern blots that neither gene is deleted in hemochromatosis. We also describe a polymorphism in one of the genes that we have previously shown to be a processed pseudogene. This polymorphism does not correlate with the presence of HC. The PIC value for this polymorphism was calculated as 0.49. 相似文献
8.
Photoaffinity labeling of scorpion toxin receptors associated with insect synaptosomal Na+ channels 总被引:1,自引:0,他引:1
M E de Lima F Couraud B Lapied M Pelhate C Ribeiro Diniz H Rochat 《Biochemical and biophysical research communications》1988,151(1):187-192
Photoreactive and radioiodinated derivatives of several scorpion toxins acting on insect Na+ channels were prepared without loss of their pharmacological activities. Photoaffinity experiments were carried out on a synaptosomal fraction from the nerve cord of the cockroach Periplaneta americana: with all toxin derivatives, a single specifically labeled band was obtained with a molecular weight of 188,000 +/- 12,000 (n = 17). These results indicate for the first time the molecular weight of the scorpion toxin receptor from the insect nervous system which is probably associated with voltage sensitive Na+ channels. One of these toxins, toxin VII from Tityus serrulatus venom, has been previously shown to be active both in mammals and in insects, in rat brain synaptosomes this toxin labeled a Mr = 31,000 +/- 4,000 band in contrast, to observations in the insect preparation. 相似文献
9.
We have studied the influence of DBA/2 non-H-2 antigens on the lethal graft-versus-host reaction (GVHR) developed across an H-2 barrier. (DBA/2 x B10.D2)F1 x B10.D2 (H-2
d) backcross (BC) mice were typed for their allelic constitution at nine genetically independent chromosome markers and used as individual cell donors simultaneously for two to three (DBA/2 X B10.D2)F1 recipients incompatible for DBA/2 non-H-2 antigens alone and two to three (DBA/2 x B10.BR)F1 recipients incompatible for DBA/2 non-H-2 antigens and H-2k. The results showed that, when compared with that developed in a control group incompatible for H-2
kalone [B10.D2(B10.D2xB10.BR)F1], the GVHR mortality seen in the presence of an additional incompatibility for DBA/2 non-H-2 antigens [(DBA/2 X B10.BR)F1recipients] is significantly delayed but only in female mice. An analysis of individual BC donors indicated that this protective effect of DBA/2 non-H-2 antigens correlates with incompatibility for gene(s) linked to the Pgm-1 chromosome marker. In contrast, incompatibility for gene(s) linked to Mod-1 and Es-3 markers accelerates GVHR mortality, but only in male mice. Finally, the results obtained with (DBA/2 x B10.D2)F1 and (DBA/2 x B10.BR)F1 recipients were compared; they showed that the intensity of the GVHR developed by cells from individual BC donors against a given set of DBA/2 non-H-2 antigens correlates well with that developed by the same BC donor against the same set of non-H-2 antigens plus H-2k. We conclude that certain non-H-2 genes (and antigens) can modulate the intensity of the GVHR developed across an H-2 barrier. The number of such genes is probably great; their effects are strong and complex, and can be sex-dependent. 相似文献
10.
Ferritin H gene polymorphism in idiopathic hemochromatosis 总被引:1,自引:1,他引:0
Véronique David Panos Papadopoulos Jacqueline Yaouanq Martine Blayau Laurent Abel Elizabetta Zappone Muriel Perichon Jim Drysdale Jean-Yves Le Gall Marcel Simon 《Human genetics》1989,82(2):123-126
Summary We have analysed karyotypes and DNA from three patients with aniridia (congenital absence of irises) and Wilms' tumour. All three had constitutional deletions from the short arm of chromosome 11. The minimum region of overlap of the deletion involves a small region of band 11p13 presumed to contain the genetic loci responsible for both phenotypic abnormalities. Using cells from these patients, somatic cell hybrids with transformed mouse cells have been prepared. Individual subclones retaining either the deletion-11 chromosome or the normal chromosome 11, in addition to a variety of other human chromosomes, have been identified. The relative position of these breakpoints have been determined and the panel of hybrids has been used to map randomly-isolated 11p13 DNA sequences. The characterisation of these deletions has provided a useful panel of hybrids for random mapping strategies designed to identify the Wilms' and aniridia genes. 相似文献