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91.
Shelness GS Hou L Ledford AS Parks JS Weinberg RB 《The Journal of biological chemistry》2003,278(45):44702-44707
We have explored the minimum sequence requirement for the initiation of apolipoprotein B (apoB)-mediated triglyceride-rich lipoprotein assembly. A series of apoB COOH-terminal truncation mutants, spanning a range from apoB34 (amino acid residues 1-1544 of apoB100) to apoB19 (residues 1-862) were transfected into COS cells with and without coexpression of the microsomal triglyceride transfer protein (MTP). ApoB34, -25, -23, -21, -20.5, and -20.1 underwent efficient conversion to buoyant lipoproteins when coexpressed with MTP. ApoB19.5 (amino acids 1-884) also directed MTP-dependent particle assembly, although at reduced efficiency. When apoB19.5 was truncated by another 22 amino acids to form apoB19, MTP-dependent lipoprotein assembly was abolished. Analysis of the lipid stoichiometry of secreted lipoproteins revealed that all apoB truncation mutants formed spherical particles containing a hydrophobic core. Even highly truncated assembly-competent forms of apoB, such as apoB19.5 and 20.1, formed lipoproteins with surface:core lipid ratios of <1. We conclude that the translation of the first approximately 884 amino acids of apoB completes a domain capable of initiating nascent lipoprotein assembly. The composition of lipids recruited into lipoproteins by this initiating domain is consistent with formation of small emulsion particles, perhaps by simultaneous desorption of both polar and neutral lipids from a saturated bilayer. 相似文献
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94.
Moore TM Shirah WB Khimenko PL Paisley P Lausch RN Taylor AE 《American journal of physiology. Lung cellular and molecular physiology》2002,283(6):L1255-L1262
Our studies show that ischemia-reperfusion (I/R) in the isolated rat lung causes retention of lymphocytes, which is associated with increased microvascular permeability, as determined by quantitative measurement of the microvascular filtration coefficient (K(f,c)). Immunoneutralization of either CD40 or CD40L, cell surface proteins important in lymphocyte-endothelial cell proinflammatory events, results in significantly lower postischemic K(f,c) values. Antagonism of CD40-CD40L signaling also results in attenuation of I/R-elicited macrophage inflammatory protein-2 production. Rat lymphocytes activated ex vivo with phorbol 12-myristate, 13-acetate increased K(f,c) in isolated lungs independently of I/R, and this increase was prevented by pretreating lungs with anti-CD40. In addition to lymphocyte involvement via CD40-CD40L interactions, our studies also show that I/R injury is potentiated by antagonism of IL-10 produced locally within the postischemic lung, whereas exogenous, rat recombinant IL-10 provided protection against I/R-induced microvascular damage. Thus acute lymphocyte involvement in lung I/R injury involves CD40-CD40L signaling mechanisms, and these events may be influenced by local IL-10 generation. 相似文献
95.
De Grey AD 《DNA and cell biology》2002,21(4):251-257
HO2*, usually termed either hydroperoxyl radical or perhydroxyl radical, is the protonated form of superoxide; the protonation/deprotonation equilibrium exhibits a pK(a) of around 4.8. Consequently, about 0.3% of any superoxide present in the cytosol of a typical cell is in the protonated form. This ratio is rather accurately reflected by the published literature on the two species, as identified by a PubMed search; at the time of writing only 28 articles mention "HO2," "hydroperoxyl" or "perhydroxyl" in their titles, as against 9228 mentioning superoxide. Here it is argued that this correlation is not justifiable: that HO2*'s biological and biomedical importance far exceeds the attention it has received. Several key observations of recent years are reviewed that can be explained much more economically when the participation of HO2* is postulated. It is suggested that a more widespread appreciation of the possible role of HO2* in biological systems would be of considerable benefit to biomedical research. 相似文献
96.
de Grey AD 《Trends in biotechnology》2002,20(11):452-455
Lysosomal degradation of damaged macromolecules is imperfect: many cell types accumulate lysosomal aggregates with age. Some such deposits are known, or are strongly suspected, to cause age-related disorders such as atherosclerosis and neurodegeration. It is possible that they also influence the rate of aging in general. Lysosomal degradation involves extensive cooperation between the participating enzymes: each generates a substrate for others until breakdown of the target material to recyclable units (such as amino acids) is complete. Hence, the age-related accumulation of lysosomal aggregates might be markedly retarded, or even reversed, by introducing just a few bacterial or fungal enzymes -'xenohydrolases' - that can degrade molecules that our natural machinery cannot. This article examines the feasibility and biomedical potential of such lysosomal enhancement as an approach to retarding or treating age-related physiological decline and disease. 相似文献
97.
Annotation of the Drosophila melanogaster euchromatic genome: a systematic review 总被引:1,自引:0,他引:1
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Misra S Crosby MA Mungall CJ Matthews BB Campbell KS Hradecky P Huang Y Kaminker JS Millburn GH Prochnik SE Smith CD Tupy JL Whitfied EJ Bayraktaroglu L Berman BP Bettencourt BR Celniker SE de Grey AD Drysdale RA Harris NL Richter J Russo S Schroeder AJ Shu SQ Stapleton M Yamada C Ashburner M Gelbart WM Rubin GM Lewis SE 《Genome biology》2002,3(12):research0083.1-8322
98.
Anita L. DeStefano L. Adrienne Cupples Kathleen S. Arnos J. H. Jr. Asher Clinton T. Baldwin Susan Blanton Melisa L. Carey Elias O. da Silva T. B. Friedman Jacquie Greenberg Anil K. Lalwani Aubrey Milunsky Walter E. Nance Arti Pandya Rajkumar S. Ramesar Andrew P. Read May Tassabejhi Edward R. Wilcox L. A. Farrer 《Human genetics》1998,102(5):499-506
Waardenburg syndrome (WS) type 1 is an autosomal dominant disorder characterized by sensorineural hearing loss, pigmentary
abnormalities of the eye, hair, and skin, and dystopia canthorum. The phenotype is variable and affected individuals may exhibit
only one or a combination of several of the associated features. To assess the relationship between phenotype and gene defect,
clinical and genotype data on 48 families (271 WS individuals) collected by members of the Waardenburg Consortium were pooled.
Forty-two unique mutations in the PAX3 gene, previously identified in these families, were grouped in five mutation categories: amino acid (AA) substitution in
the paired domain, AA substitution in the homeodomain, deletion of the Ser-Thr-Pro-rich region, deletion of the homeodomain
and the Ser-Thr-Pro-rich region, and deletion of the entire gene. These mutation classes are based on the structure of the
PAX3 gene and were chosen to group mutations predicted to have similar defects in the gene product. Association between mutation
class and the presence of hearing loss, eye pigment abnormality, skin hypopigmentation, or white forelock was evaluated using
generalized estimating equations, which allowed for incorporation of a correlation structure that accounts for potential similarity
among members of the same family. Odds for the presence of eye pigment abnormality, white forelock, and skin hypopigmentation
were 2, 8, and 5 times greater, respectively, for individuals with deletions of the homeodomain and the Pro-Ser-Thr-rich region
compared to individuals with an AA substitution in the homeodomain. Odds ratios that differ significantly from 1.0 for these
traits may indicate that the gene products resulting from different classes of mutations act differently in the expression
of WS. Although a suggestive association was detected for hearing loss with an odds ratio of 2.6 for AA substitution in the
paired domain compared with AA substitution in the homeodomain, this odds ratio did not differ significantly from 1.0.
Received: 27 July 1997 / Accepted: 9 December 1997 相似文献
99.
Aubrey Gorbman 《Acta zoologica》1999,80(4):301-305
The vertebrate hypothalamo-hypophyseal neurosecretory system is a complex anatomical device for central nervous control over secretion of pituitary hormones. Since it is present in the most primitive vertebrates, the cyclostomes, it is of interest to look for a possible invertebrate anatomical equivalent, or precursor, for clues as to its evolution. We have found in six species of amphioxus, members of an invertebrate group (cephalochordates), considered to be closest to the vertebrates, that there is a morphologically equivalent neuro-epithelial complex, that in many ways resembles the hypothalamo-hypophyseal system of vertebrates. In the six amphioxus species described here the nervous element is a ventral lobe of the brain, the infundibulum, that extends downward along the right side of the notochord, and ends near the dorsal surface of a Rathke's pouch-like structure known as Hatschek's pit. This part of Hatschek's pit has been found earlier to contain a vertebrate LH-like gonadotropin. Therefore, the infundibulum-Hatschek's pit system of amphioxus may be involved in regulating the seasonal reproductive cycle, and it appears to be a direct homologue of the vertebrate hypothalamo-hypophyseal neurosecretory system functionally as well as morphologically. 相似文献
100.
Ultrastructure of the ovary of the Pacific hagfish was studied. Attention was paid to the mesovarium, small oocytes, oocytes of intermediate size, large oocytes, postovulatory follicles shortly after ovulation, postovulatory follicles considerably after ovulation, and preovulatory atretic follicles. The progressive changes of thecal and granulosa layers in the course of egg development and degeneration are described. No cells showing the ultrastructural characteristics associated with steroidogenesis were found. 相似文献