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81.
Haidari M Leung N Mahbub F Uffelman KD Kohen-Avramoglu R Lewis GF Adeli K 《The Journal of biological chemistry》2002,277(35):31646-31655
Insulin-resistant states are characterized by hypertriglyceridemia, predominantly because of overproduction of hepatic very low density lipoprotein particles. The additional contribution of intestinal lipoprotein overproduction to the dyslipidemia of insulin-resistant states has not been previously appreciated. Here, we have investigated intestinal lipoprotein production in a fructose-fed hamster model of insulin resistance previously documented to have whole body and hepatic insulin resistance, and hepatic very low density lipoprotein overproduction. Chronic fructose feeding for 3 weeks induced significant oversecretion of apolipoprotein B48 (apoB48)-containing lipoproteins in the fasting state and during steady state fat feeding, based on (a) in vivo Triton WR1339 studies of apoB48 production as well as (b) ex vivo pulse-chase labeling of intestinal enterocytes from fasted and fed hamsters. ApoB48 particle overproduction was accompanied by increased intracellular apoB48 stability, enhanced lipid synthesis, higher abundance of microsomal triglyceride transfer protein mass, and a significant shift toward the secretion of larger chylomicron-like particles. ApoB48 particle overproduction was not observed with short-term fructose feeding or in vitro incubation of enterocytes with fructose. Secretion of intestinal apoB48 and triglyceride was closely linked to intestinal enterocyte de novo lipogenesis, which was up-regulated in fructose-fed hamsters. Inhibition of fatty acid synthesis by cerulenin, a fatty acid synthase inhibitor, resulted in a dose-dependent decrease in intestinal apoB48 secretion. Overall, these findings further suggest that intestinal overproduction of apoB48 lipoproteins should also be considered as a major contributor to the fasting and postprandial dyslipidemia observed in response to chronic fructose feeding and development of an insulin-resistant state. 相似文献
82.
BACKGROUND: The incretin hormones GIP and GLP-1 are thought to be produced in separate endocrine cells located in the proximal and distal ends of the mammalian small intestine, respectively. METHODS AND RESULTS: Using double immunohistochemistry and in situ hybridization, we found that GLP-1 was colocalized with either GIP or PYY in endocrine cells of the porcine, rat, and human small intestines, whereas GIP and PYY were rarely colocalized. Thus, of all the cells staining positively for either GLP-1, GIP, or both, 55-75% were GLP-1 and GIP double-stained in the mid-small intestine. Concentrations of extractable GIP and PYY were highest in the midjejunum [154 (95-167) and 141 (67-158) pmol/g, median and range, respectively], whereas GLP-1 concentrations were highest in the ileum [92 (80-207) pmol/l], but GLP-1, GIP, and PYY immunoreactive cells were found throughout the porcine small intestine. CONCLUSIONS: Our results provide a morphological basis to suggest simultaneous, rather than sequential, secretion of these hormones by postprandial luminal stimulation. 相似文献
83.
Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis 总被引:20,自引:0,他引:20
Schaible UE Winau F Sieling PA Fischer K Collins HL Hagens K Modlin RL Brinkmann V Kaufmann SH 《Nature medicine》2003,9(8):1039-1046
Protective immunity against Mycobacterium tuberculosis involves major histocompatibility complex class I (MHC-I)- and CD1-restricted CD8 T cells, but the mechanisms underlying antigen delivery to antigen-presenting molecules remain enigmatic. Macrophages, the primary host cells for mycobacteria, are CD1-negative. Here we show that M. tuberculosis phagosomes are secluded from the cytosolic MHC-I processing pathway and that mycobacteria-infected cells lose their antigen-presenting capacity. We also show that mycobacteria induce apoptosis in macrophages, causing the release of apoptotic vesicles that carry mycobacterial antigens to uninfected antigen-presenting cells (APCs). Inhibition of apoptosis reduced transfer of antigens to bystander cells and activation of CD8 T cells. Uninfected dendritic cells, which engulfed extracellular vesicles, were indispensable for subsequent cross-presentation of antigens, through MHC-I and CD1b, to T cells from mycobacteria-sensitized donors. This new 'detour' pathway for presentation of antigens from a phagosome-contained pathogen shows the functional significance of infection-induced apoptosis in the activation of CD8 T cells specific for both protein and glycolipid antigens in tuberculosis. 相似文献
84.
Pathogens or pathogen-associated molecular patterns can signal to cells of the innate immune system and trigger effective adaptive immunity. However, relatively little is known about how the innate immune system detects tissue injury or necrosis. Evidence suggests that the release of heat-shock proteins (HSPs) may provide adjuvant-like signals, but the ability of HSPs to promote activation or tolerance in vivo has not been addressed. In this study we show that Hsp70 promotes dendritic cell (DC) function and, together with antigen, triggers autoimmune disease in vivo. 相似文献
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87.
Great-tailed grackles (Quiscalus mexicanus) are sexually dimorphic,dichromatic, colonially nesting blackbirds. In this study, males
pursued three basic types of conditional mating strategies,each of which employed a different set of mating tactics. Territorialmales defended one or more trees in which several females nested.They achieved reproductive success by siring the offspringof their social mates and through extrapair fertilization.Resident males lived in the colony but did not defend territoriesor have social mates. Transient males passed through the colony,
staying no more than a few days, and probably visited more thanone colony. Residents appeared to queue for access to territories,but transients did not. Residents and transients gained allpaternity through extrapair fertilizations and provided noparental care. Territorial males sired the majority of offspring,but residents and transients also sired small numbers of nestlings.
Territorial males were larger and had longer tails than nonterritorialmales. The number of social mates was related to body size,and males that sired nestlings were heavier and had longertails than males with no genetic reproductive success. Malesthat gained paternity through extrapair fertilization wereheavier and had longer tails than males that did not. The matingsystem of great-tailed grackles can best be categorized as
"non-faithful-female frank polygyny." 相似文献
88.
Kathryn Gill Nicolas Desaulniers Paule Desjardins Kristine Lake 《Mammalian genome》1998,9(12):929-935
The purpose of the present study was to characterize the C57BL/6J, A/J, and AXB/BXA Recombinant Inbred (RI) strains of mice
for voluntary alcohol consumption. Quantitative Trait Locus (QTL) analysis was used to provide provisional location of QTLs
for alcohol consumption. The inbred strains were screened for levels of alcohol intake (calculated as alcohol preference and
absolute alcohol consumption) by receiving 4 days of forced exposure to a 10% (wt/vol) solution of alcohol, followed by 3
weeks of free choice between water and 10% alcohol. A wide and continuous distribution of values for alcohol consumption and
preference was obtained in the AXB/BXA RI strains, confirming polygenic influences on alcohol-related behaviors. Significant
gender differences were found for both alcohol preference [F28,651= 2.12, p < 0.001] and absolute alcohol consumption [F28,647= 2.57, p < 0.001]. In males, putative QTLs were mapped to chromosomes (Chrs) 2, 5, 7, 10, 11, and 16. Multiple regression analysis
indicated that approximately 75% of the genetic variance in alcohol preference in males could be accounted for by three of
the QTL regions. Several of the putative QTLs appeared to be male-specific (Tyr on Chr 7; D10Mit126 on Chr 10; D11Mit61 on Chr 11). In females, seven putative QTLs were mapped to Chrs 2, 4, 5, 7, 11, 16, and 19. Approximately 90% of the genetic
variance in alcohol preference in females could be accounted for by four QTL regions, as determined by multiple regression.
The QTL on Chr 11 near D11Mit35 appeared to be female-specific. This site was close to a female-specific QTL (Alcp2) previously mapped in C57BL/6J × DBA/2J backcrosses by Melo and coworkers (Nat Genet 13, 147, 1996). The QTLs mapped for
alcohol preference in the present study must be considered suggestive at the present time, since only D2Mit74 met very strict statistical criteria for significance. However, the concordance across several studies for the loci on Chrs
2, 4, 7, 9, and 11 suggest that some common QTLs influencing alcohol preference have been identified. Confirmation of QTLs
mapped in the present study is currently being conducted in a new series of recombinant congenic (RC) strains developed from
reciprocal backcrosses between the A/J and C57BL/6J progenitors. The concomitant use of both RI and RC strains developed from
the same progenitors should provide a powerful means of detecting, confirming, and mapping QTLs for alcohol-related traits.
Received: 25 August 1998 / Accepted: 8 October 1998 相似文献
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90.
Nancy Witowski Elizabeth Lusczek Charles Determan Jr. Daniel Lexcen Kristine Mulier Beverly Ostrowski Greg Beilman 《PloS one》2015,10(4)