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101.
Sevilla C Bourret P Noguès C Moatti JP Sobol H Julian-Reynier C;Groupe Génétique et Cancer 《Médecine sciences : M/S》2004,20(8-9):788-792
One example of the recent advances of scientific research on the human genome is the identification of two susceptibility genes to breast/ovarian cancer, BRCA1 and BRCA2, making possible the introduction in medical practices of genetic testing to detect patients with an increased risk of developing such cancers. In this context of diffusion, two surveys were carried out to appraise the activity profiles in 1998 and in 2001 of all the different participants in those new medical practices in France, physicians in charge of genetic counselling, medical centres where consultations take place and laboratories. Results show that over the period 1998-2001, few changes occurred, mainly the reduction of the average waiting time to get the result of a genetic test, the increase in the annual number of BRCA2 families identified to a level similar to the one of BRCA1 and the automation of the biological analyses without noting a considerable increase in the annual output of laboratories till 2001 however. This surprising moderate evolution must be connected to the existence of some particular external factors making the framework of the development of these new medical and biological practices and their future really uncertain. The diffusion of BRCA1/2 genetic testing has been carried out facing the traditional difficulties of any innovating activities, but also the uncertainties related to intellectual property rights on genes and the reimbursement of genetic counselling and biological testing. These uncertainties have certainly restrained the pace of change as many actors in this field have opted for a wait and see strategy bearing in mind the possible future constraints imposed to their future activity, especially if European patents on the BRCA1/2 genes are finally granted by the European patent office (EPO). 相似文献
102.
Y Nakamura C G Mathew H Sobol D F Easton H Telenius T Bragg K Chin J Clark C Jones G M Lenoir 《Genomics》1989,5(2):199-203
The inherited cancer syndrome multiple endocrine neoplasia type 2A (MEN2A) has recently been mapped to chromosome 10. We have typed 29 families with this disorder with DNA markers from the pericentromeric region of chromosome 10. Two markers, RBP3 and MCK2, were tightly linked to the MEN2A gene at recombination fractions of less than 3%. Multipoint analysis of the linkage data suggests that the gene is located within a 3-cM interval defined by the markers RBP3/MCK2 on one side and TB14.34 on the other. No evidence for locus heterogeneity was detected in any of the 27 families from 14 countries who were informative for the markers tested. The data confirm and refine the original assignment and provide the basis for presymptomatic screening for this disorder. 相似文献
103.
104.
Phosphorothioate analogues of (2'-5')(A)4: agonist and antagonist activities in intact cells 总被引:1,自引:0,他引:1
G Charachon R W Sobol C Bisbal T Salehzada M Silhol R Charubala W Pfleiderer B Lebleu R J Suhadolnik 《Biochemistry》1990,29(10):2550-2556
Metabolically stable phosphorothioate tetramer analogues of (2'-5')(A)n with Rp and/or Sp chirality in the 2'-5'-phosphodiester linkages constitute a new class of antiviral agents since they mimic the effects of interferons. Three of the diastereomeric 5'-monophosphates (i.e., pRpRpRp, pSpRpRp, and pRpSpSp) bind to and activate RNase L from extracts of HeLa cells. However, the pSpSpSp (2'-5')-(A)4-phosphorothioate is unique in that it binds to, but cannot activate, RNase L to cleave rRNA. When microinjected into the cytoplasm of HeLa cells followed by virus infection, the pRpRpRp, pSpRpRp, and pRpSpSp (2'-5')(A)4-phosphorothioates demonstrate antiviral activity, as does (2'-5')(A)4ox-red, an active (2'-5')(A)n analogue. When microinjected simultaneously with (2'-5')(A)nox-red, an active the pSpSpSp (2'-5')(A)4-phosphorothioate inhibits activation of RNase L in HeLa cells, thereby blocking direct protection of vesicular stomatitis virus. The agonist and antagonist properties of pRpRpRp and pSpSpSp, respectively, are transient probably as a consequence of the hydrolysis of the 5'-monophosphate and formation of the less active (2'-5')(A)4-phosphorothioate cores. The possible use of these (2'-5')(A)4-phosphorothioates as tools for dissecting the biological significance of the (2'-5')(A)n system or in antiviral chemotherapy is discussed. 相似文献
105.
Alexander G. Sobol Alexander S. Arseniev Galina V. Abdulaeva Larisa Yu. Musina Vladimir F. Bystrov 《Journal of biomolecular NMR》1992,2(2):161-171
Summary The conformation of chymotryptic fragment C2 of bacteriorhodopsin (residues 1–71) was studied by 2D1H NMR. The fragment was solubilized in a mixture of chloroform/methanol (11), 0.1 M LiClO4. Most of the resonances in1H NMR spectra of fragment C2 were assigned using phase-sensitive DQF-COSY, TOCSY, and NOESY techniques. To simplify the assignment procedure for overlapping regions of NMR spectra, an analog of fragment C2 with leucines deuterated in -positions was used. Deuterium exchange rates for amide protons were measured in a series of TOCSY spectra. Two right-handed -helical regions Pro8-Lys30 and Lys41-Leu62 were identified on the basis of NOE connectivities and deuterium exchange rates. The N-terminal part of the fragment (Ala.2-Gly6) adopts the helical conformation stabilized by 3 hydrogen bonds. 相似文献
106.
Hermine O Lortholary O Leventhal PS Catteau A Soppelsa F Baude C Cohen-Akenine A Palmérini F Hanssens K Yang Y Sobol H Fraytag S Ghez D Suarez F Barete S Casassus P Sans B Arock M Kinet JP Dubreuil P Moussy A 《PloS one》2008,3(5):e2266
Background
Indolent forms of mastocytosis account for more than 90% of all cases, but the types and type and severity of symptoms and their impact on the quality of life have not been well studied. We therefore performed a case-control cohort study to examine self-reported disability and impact of symptoms on the quality of life in patients with mastocytosis.Methodology/Principal Findings
In 2004, 363 mastocytosis patients and 90 controls in France were asked to rate to their overall disability (OPA score) and the severity of 38 individual symptoms. The latter was used to calculate a composite score (AFIRMM score). Of the 363 respondents, 262 were part of an ongoing pathophysiological study so that the following data were available: World Health Organization classification, standard measures of physical and psychological disability, existence of the D816V KIT mutation, and serum tryptase level. The mean OPA and AFIRMM scores and the standard measures of disability indicated that most mastocytosis patients suffer from disabilities due to the disease. Surprisingly, the patient''s measurable and perceived disabilities did not differ according to disease classification or presence or absence of the D816V KIT mutation or an elevated (≥20 ng/mL) serum tryptase level. Also, 32 of the 38 AFIRMM symptoms were more common in patients than controls, but there were not substantial differences according to disease classification, presence of the D816V mutation, or the serum tryptase level.Conclusions
On the basis of these results and for the purposes of treatment, we propose that mastocytosis be first classified as aggressive or indolent and that indolent mastocytosis then be categorized according to the severity of patients'' perceived symptoms and their impact on the quality of life. In addition, it appears that mastocytosis patients suffer from more symptoms and greater disability than previously thought, that mastocytosis may therefore be under-diagnosed, and that the symptoms of the indolent forms of mastocytosis might be due more to systemic release of mediators than mast cell burden. 相似文献107.
C.?V.?Sobol V.?P.?NesterovEmail author G.?B.?Belostotskaya S.?M.?Korotkov 《Biophysics》2017,62(1):68-74
The effects of Т1+ ions on the dynamics of intracellular Cа2+ in neonatal rat cardiomyocytes have been studied. It was shown for the first time that application of Т1+ led to an uncontrolled increase in [Cа2+]i in cells. Moreover, the ability of Т1+ to increase [Cа2+]i depended on the Т1+ concentration used and the time of exposure to the cells. The increase in [Cа2+]i was related to the entry of Cа2+ from the extracellular medium. Thallium did not release Cа2+ from intracellular stores. The thallium-induced increase in [Cа2+]i was not inhibited by nifedipine. It is possible that L-channels do not participate in the processes of thalliuminduced increase in [Cа2+]i. It is assumed that the thallium ions-induced calcium overload in cardiomyocytes may contribute to the toxic effect of Т1+ on the myocardium. 相似文献
108.
Katsuhiko Yoshizawa Elena Jelezcova Ashley R. Brown Julie F. Foley Abraham Nyska Xiangli Cui Lorne J. Hofseth Robert M. Maronpot Samuel H. Wilson Antonia R. Sepulveda Robert W. Sobol 《PloS one》2009,4(8)
Background
Altered expression of DNA polymerase β (Pol β) has been documented in a large percentage of human tumors. However, tumor prevalence or predisposition resulting from Pol β over-expression has not yet been evaluated in a mouse model.Methodology/Principal Findings
We have recently developed a novel transgenic mouse model that over-expresses Pol β. These mice present with an elevated incidence of spontaneous histologic lesions, including cataracts, hyperplasia of Brunner''s gland and mucosal hyperplasia in the duodenum. In addition, osteogenic tumors in mice tails, such as osteoma and osteosarcoma were detected. This is the first report of elevated tumor incidence in a mouse model of Pol β over-expression. These findings prompted an evaluation of human gastrointestinal tumors with regard to Pol β expression. We observed elevated expression of Pol β in stomach adenomas and thyroid follicular carcinomas, but reduced Pol β expression in esophageal adenocarcinomas and squamous carcinomas.Conclusions/Significance
These data support the hypothesis that balanced and proficient base excision repair protein expression and base excision repair capacity is required for genome stability and protection from hyperplasia and tumor formation. 相似文献109.
110.
Steven A. Narod Hagay Sobol Isabelle Schuffenecker Marie-France Lavoué Gilbert M. Lenoir 《Human genetics》1991,86(5):529-531
Summary We have examined 30 families with multiple endocrine neoplasia type 2a (MEN2A). Linkage studies indicate that the gene for MEN2A is located on chromosome 10, tightly linked to the D10Z1 locus. 相似文献