全文获取类型
收费全文 | 1140篇 |
免费 | 128篇 |
出版年
2022年 | 11篇 |
2021年 | 32篇 |
2020年 | 12篇 |
2019年 | 15篇 |
2018年 | 24篇 |
2017年 | 21篇 |
2016年 | 37篇 |
2015年 | 53篇 |
2014年 | 51篇 |
2013年 | 55篇 |
2012年 | 65篇 |
2011年 | 60篇 |
2010年 | 45篇 |
2009年 | 58篇 |
2008年 | 47篇 |
2007年 | 36篇 |
2006年 | 39篇 |
2005年 | 38篇 |
2004年 | 35篇 |
2003年 | 34篇 |
2002年 | 33篇 |
2001年 | 30篇 |
2000年 | 31篇 |
1999年 | 22篇 |
1998年 | 15篇 |
1997年 | 8篇 |
1996年 | 13篇 |
1995年 | 8篇 |
1994年 | 9篇 |
1993年 | 9篇 |
1992年 | 28篇 |
1991年 | 24篇 |
1990年 | 30篇 |
1989年 | 32篇 |
1988年 | 18篇 |
1987年 | 20篇 |
1986年 | 18篇 |
1985年 | 18篇 |
1984年 | 17篇 |
1983年 | 12篇 |
1982年 | 11篇 |
1981年 | 6篇 |
1980年 | 12篇 |
1979年 | 13篇 |
1978年 | 14篇 |
1977年 | 10篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1972年 | 5篇 |
1968年 | 4篇 |
排序方式: 共有1268条查询结果,搜索用时 15 毫秒
971.
Kernstine KH Andersen ES Falabella A Ramirez NA Anderson CA Beblawi I 《Innovations (Philadelphia, Pa.)》2009,4(6):354-357
Esophageal leiomyomas are resected in symptomatic and/or malignancy-suspicious cases. Traditionally, they have been removed by laparotomy or thoracotomy and more recently by thoracoscopy and laparoscopy. Mucosal injury is reported as high as 7% of cases but may be higher in unreported general practice. Robotic technology seems to offer advantages. We describe a robotic approach that seems to minimize mobilization of the esophagus, potentially decreasing the likelihood of mucosal injury and postoperative recovery time. We review the literature to evaluate the reports of mucosal injury with the open, minimally invasive, and robotic techniques and describe our own method. To improve efficiency, we use a four-arm technique. 相似文献
972.
Uroporphyrinogen III synthase knock-in mice have the human congenital erythropoietic porphyria phenotype, including the characteristic light-induced cutaneous lesions 下载免费PDF全文
Bishop DF Johansson A Phelps R Shady AA Ramirez MC Yasuda M Caro A Desnick RJ 《American journal of human genetics》2006,78(4):645-658
Congenital erythropoietic porphyria (CEP), an autosomal recessive inborn error, results from the deficient but not absent activity of uroporphyrinogen III synthase (URO-synthase), the fourth enzyme in the heme biosynthetic pathway. The major clinical manifestations include severe anemia, erythrodontia, and disfiguring cutaneous involvement due to the accumulation of phototoxic porphyrin I isomers. Murine models of CEP could facilitate studies of disease pathogenesis and the evaluation of therapeutic endeavors. However, URO-synthase null mice were early embryonic lethals. Therefore, knock-in mice were generated with three missense mutations, C73R, V99A, and V99L, which had in vitro-expressed activities of 0.24%, 5.9%, and 14.8% of expressed wild-type activity, respectively. Homozygous mice for all three mutations were fetal lethals, except for mice homozygous for a spontaneous recombinant allele, V99A(T)/V99A(T), a head-to-tail concatemer of three V99A targeting constructs. Although V99A(T)/V99A(T) and C73R/V99A(T) mice had approximately 2% hepatic URO-synthase activity and normal hepatic microsomal heme and hemoprotein levels, they had 20% and 13% of wild-type activity in erythrocytes, respectively, which indicates that sufficient erythroid URO-synthase was present for fetal development and survival. Both murine genotypes showed marked porphyrin I isomer accumulation in erythrocytes, bone, tissues, and excreta and had fluorescent erythrodontia, hemolytic anemia with reticulocytosis and extramedullary erythropoiesis, and, notably, the characteristic light-induced cutaneous involvement. These mice provide insight into why CEP is an erythroid porphyria, and they should facilitate studies of the disease pathogenesis and therapeutic endeavors for CEP. 相似文献
973.
Dhanasekaran Shanmugam Bo Wu Ursula Ramirez Eileen K. Jaffe David S. Roos 《The Journal of biological chemistry》2010,285(29):22122-22131
Apicomplexan parasites (including Plasmodium spp. and Toxoplasma gondii) employ a four-carbon pathway for de novo heme biosynthesis, but this pathway is distinct from the animal/fungal C4 pathway in that it is distributed between three compartments: the mitochondrion, cytosol, and apicoplast, a plastid acquired by secondary endosymbiosis of an alga. Parasite porphobilinogen synthase (PBGS) resides within the apicoplast, and phylogenetic analysis indicates a plant origin. The PBGS family exhibits a complex use of metal ions (Zn2+ and Mg2+) and oligomeric states (dimers, hexamers, and octamers). Recombinant T. gondii PBGS (TgPBGS) was purified as a stable ∼320-kDa octamer, and low levels of dimers but no hexamers were also observed. The enzyme displays a broad activity peak (pH 7–8.5), with a Km for aminolevulinic acid of ∼150 μm and specific activity of ∼24 μmol of porphobilinogen/mg of protein/h. Like the plant enzyme, TgPBGS responds to Mg2+ but not Zn2+ and shows two Mg2+ affinities, interpreted as tight binding at both the active and allosteric sites. Unlike other Mg2+-binding PBGS, however, metal ions are not required for TgPBGS octamer stability. A mutant enzyme lacking the C-terminal 13 amino acids distinguishing parasite PBGS from plant and animal enzymes purified as a dimer, suggesting that the C terminus is required for octamer stability. Parasite heme biosynthesis is inhibited (and parasites are killed) by succinylacetone, an active site-directed suicide substrate. The distinct phylogenetic, enzymatic, and structural features of apicomplexan PBGS offer scope for developing selective inhibitors of the parasite enzyme based on its quaternary structure characteristics. 相似文献
974.
A series of cholesterol (Chol) probes with NBD and Dansyl fluorophores attached to the 3-hydroxyl position via carbamate linkers has been designed and synthesized and their ability to mimic the behavior of natural cholesterol in bilayer membranes has been examined. Fluorescence spectroscopy data indicate that the NBD-labeled lipids are located in the polar headgroup region of the bilayer with their position varying with the method of fluorophore attachment and the linker length. The partitioning of the Chol probes between liquid-ordered (Lo) and liquid-disordered (Lo) phases in supported bilayers prepared from ternary lipid mixtures of DOPC, Chol and either egg sphingomyelin or DPPC was examined by fluorescence microscopy. The carbamate-linked NBD-Chols show a stronger preference for partitioning into Lo domains than does a structurally similar probe with an ester linkage, indicating the importance of careful optimization of probe and linker to provide the best Chol mimic. Comparison of the partitioning of NBD probes to literature data for native Chol indicates that the probes reproduce well the modest enrichment of Chol in Lo domains as well as the ceramide-induced displacement of Chol. One NBD probe was used to follow the dynamic redistribution of Chol in phase separated membranes in response to in situ ceramide generation. This provides the first direct optical visualization of Chol redistribution during enzymatic ceramide generation and allows the assignment of new bilayer regions that exclude dye and have high lateral adhesion to ceramide-rich regions. 相似文献
975.
Oliveira-Silva MB Lages-Silva E Resende DV Prata A Ramirez LE Frenkel JK 《Experimental parasitology》2006,114(3):189-192
Intracellular development of Cystoisospora belli was demonstrated in 4 different mammalian cell lines. Human ileocecal adenocarcinoma (HCT-8), epithelial carcinoma of lung (A549), Madin-Darby bovine kidney (MDBK), and African green monkey kidney (VERO) were exposed in vitro to C. belli sporozoites, which had been isolated from the feces of HIV-AIDS patients. Parasites invaded all the cellular types between 4 and 12h after exposure and multiplication was demonstrated after 24 h. Grater number of merozoites formed in VERO cells, followed by HCT-8. In the MDBK and HCT-8 cells, the parasitophorous vacuole was less evident and immobile merozoites were observed in the cytoplasm. In VERO cells, one or several parasitophorous vacuoles contained up to 16 mobile sporozoites. No oocysts were found in any of the cell types used. VERO cells may be suitable for studies of the interaction between parasite and host cells. 相似文献
976.
Arista S Giammanco GM De Grazia S Ramirez S Lo Biundo C Colomba C Cascio A Martella V 《Journal of virology》2006,80(21):10724-10733
A rotavirus sample collection from 19 consecutive years was used to investigate the heterogeneity and the dynamics of evolution of G1 rotavirus strains in a geographically defined population. Phylogenetic analysis of the VP7 gene sequences of G1P[8] human rotavirus strains showed the circulation of a heterogeneous population comprising three lineages and seven sublineages. Increases in the circulation of G1 rotaviruses were apparently associated with the introduction of novel G1 strains that exhibited multiple amino acid changes in antigenic regions involved in rotavirus neutralization compared to the strains circulating in the previous years. The emergence and/or introduction of G1 antigenic variants might be responsible for the continuous circulation of G1 rotaviruses in the local population, with the various lineages and sublineages appearing, disappearing, or cocirculating in an alternate fashion under the influence of immune-pressure mechanisms. Sequence analysis of VP4-encoding genes of the G1 strains revealed that the older strains were associated with a unique VP4 lineage, while a novel VP4 lineage emerged after 1995. The introduction of human rotavirus vaccines might alter the forces and balances that drive rotavirus evolution and determine the spread of novel strains that are antigenically different from those included in the vaccine formulations. The continuous emergence of VP7-VP4 gene combinations in human rotavirus strains should be taken into consideration when devising vaccination strategies. 相似文献
977.
Kapan DD Flanagan NS Tobler A Papa R Reed RD Gonzalez JA Restrepo MR Martinez L Maldonado K Ritschoff C Heckel DG McMillan WO 《Genetics》2006,173(2):735-757
We report a dense genetic linkage map of Heliconius erato, a neotropical butterfly that has undergone a remarkable adaptive radiation in warningly colored mimetic wing patterns. Our study exploited natural variation segregating in a cross between H. erato etylus and H. himera to localize wing color pattern loci on a dense linkage map containing amplified fragment length polymorphisms (AFLP), microsatellites, and single-copy nuclear loci. We unambiguously identified all 20 autosomal linkage groups and the sex chromosome (Z). The map spanned a total of 1430 Haldane cM and linkage groups varied in size from 26.3 to 97.8 cM. The average distance between markers was 5.1 cM. Within this framework, we localized two major color pattern loci to narrow regions of the genome. The first gene, D, responsible for red/orange elements, had a most likely placement in a 6.7-cM region flanked by two AFLP markers on the end of a large 87.5-cM linkage group. The second locus, Sd, affects the melanic pattern on the forewing and was found within a 6.3-cM interval between flanking AFLP loci. This study complements recent linkage analysis of H. erato's comimic, H. melpomene, and forms the basis for marker-assisted physical mapping and for studies into the comparative genetic architecture of wing-pattern mimicry in Heliconius. 相似文献
978.
S Rainier M K Jain F Ramirez P V Ioannou J F Marecek R Wagner 《Biochimica et biophysica acta》1979,558(2):187-198
Synthesis and phase transition chaaracteristics of aqueous dispersions of the homologous (12 : 0, 14 : 0, 16 : 0) diphosphatidylglycerols (cardiolipins) and phosphatidyldiacylglycerols are reported. Electron microscopy of the negatively stained aqueous dispersions reveals a characteristic lamellar structure suggesting that these phospholipid molecules are organized as bilayers in the aqueous dispersions. The phase transition temperature (Tm) and the enthalpy of transition (delta H) increase monotonically with chain length in the cardiolipin and phosphatidyldiacylglycerol series; Tm for phosphatidyldiacylglycerol is higher than that for cardiolipin of the same chain-length. The transition temperatures for the enantiomeric sn-3,3- and sn-1,1-phosphatidyldiacylglycerol and for the diastereomeric, meso-sn-1,3-phosphatidyldiacylglycerol are approximately the same. The molar enthalpy for the transition of cardiolipin-NH+4 bilayers is approximately twice the value for the phosphatidylcholines of the same chain length, i.e., the molar enthalpy per acyl chain is approximately the same in the two systems. The transition temperatures for metal ion salts of C16-cardiolipin exhibit a biphasic dependence upon the unhydrated ionic radii, i.e., the highest Tm is observed for Ca2+-cardiolipin and decreases for the salts of ions with smaller and larger ionic radii than that of Ca2+. The lowest Tm is observed for Rb+-cardiolipin. Monovalent metal salts of cardiolipin exhibit two phase transitions. This effect may result from different conformational packing of the four acyl chains due to differences in metal-phosphate binding. 相似文献
979.
980.
M Es-souni P Bournot J P Berlot L C Ramirez 《The Journal of steroid biochemistry and molecular biology》1991,38(4):483-488
The expression of 19-hydroxylase activity in the Y1 adrenal cell line is reported here for the first time. Two new metabolites from the incubation of deoxycorticosterone (DOC) with these cells, 19-hydroxy-20 alpha-dihydroDOC and 19-hydroxy-20 alpha-dihydrocorticosterone, have been identified. The most important of the two is the 11 beta,19-dihydroxylated metabolite, which is produced in smaller amounts than 18-hydroxy-20 alpha-dihydrocorticosterone. A third 19-hydroxylated metabolite was identified as 19-hydroxy-20 alpha-dihydroprogesterone, produced from the cholesterol in the serum supplemented medium. These results show that the cytochrome P-450(11)beta of this cell line expresses 19-hydroxylase activity in addition to 11 beta- and 18-hydroxylase activities, as do those of other species. 相似文献