全文获取类型
收费全文 | 1025篇 |
免费 | 107篇 |
出版年
2023年 | 5篇 |
2022年 | 12篇 |
2021年 | 24篇 |
2020年 | 16篇 |
2019年 | 23篇 |
2018年 | 25篇 |
2017年 | 19篇 |
2016年 | 44篇 |
2015年 | 55篇 |
2014年 | 69篇 |
2013年 | 90篇 |
2012年 | 91篇 |
2011年 | 83篇 |
2010年 | 58篇 |
2009年 | 37篇 |
2008年 | 68篇 |
2007年 | 51篇 |
2006年 | 38篇 |
2005年 | 47篇 |
2004年 | 48篇 |
2003年 | 50篇 |
2002年 | 50篇 |
2001年 | 9篇 |
2000年 | 10篇 |
1999年 | 10篇 |
1998年 | 11篇 |
1997年 | 10篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 2篇 |
1993年 | 7篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1983年 | 2篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1979年 | 5篇 |
1977年 | 5篇 |
1976年 | 2篇 |
1936年 | 1篇 |
1932年 | 3篇 |
1931年 | 2篇 |
1929年 | 3篇 |
1926年 | 1篇 |
1925年 | 1篇 |
1924年 | 1篇 |
1920年 | 2篇 |
排序方式: 共有1132条查询结果,搜索用时 31 毫秒
11.
Expression of HLA-B27 in transgenic mice is controlled by gene(s) mapping between H-2D and H-2L loci 总被引:2,自引:0,他引:2
The level of HLA-B27 transgene expression on the cell surface is dependent on the host H-2 haplotype. Mice homozygous for the H-2
b
, H-2
f
, H-2
f
, H-2
p
, H-2
r
, and H-2
k
haplotypes express B27 at high levels. An intermediate level of B27 expression is observed in H-2
v
mice whereas low levels of B27 are expressed in H-2
q
and H-2
d
mice. The decreased expression of B27 maps to the D region of the major histocompatibility complex. Recombinant strain B10.RKDB (DdLb) mapped the low expression gene centromeric to H-2L. In order to determine the low expression within the H-2D region, the B27 transgene was introduced into B10.D2-H-2
dm1
and BALB/c-H-2
dm2
mice. Expression of B27 in both of these strains was high indicating that neither H-2D
d
nor H-2L
d
is responsible for the low expression. This maps the effect between the H-2D and H-2L loci. In addition, introduction of human 2-microglobulin (2m) into B10.D2-B27 transgenic mice caused a marked enhancement of B27 expression on the cell surface suggesting that the defect in B27 expression in certain haplotypes is due to an inability of B27 to associate with endogenous mouse 2m. We propose that gene(s) mapping between D and L (either D2, D3, D4, or some as yet unidentified gene) may be involved in class I assembly by helping association of 2m with class I. This putative molecule, designated Assembly Enhancer (AE) might have a negative influence in the association between human class II and mouse 2m. 相似文献
12.
D. James Morr V. Schirrmacher Peter Robinson Kristine Hess Werner W. Franke 《Experimental cell research》1979,119(2):265-275
Purified fractions of plasma membrane, Golgi apparatus, rough endoplasmic reticulum vesicles, nuclear envelope, and mitochondria were isolated from mouse liver and the distribution of H-2 histocompatibility antigens determined by indirect radioimmunoassay before and after membrane disruptive treatments. Fractions enriched in plasma membrane (surface membrane) revealed H-2 antigens in highest concentration; disruptive treatments were not necessary to reveal H-2 antigens with surface membranes. In contrast, internal membranes did not possess H-2 antigens which were accessible to antibody. Golgi apparatus fractions or some component of these fractions (e.g. secretory vesicles) possessed the antigens but in a latent form where accessibility was provided by simple rupture of the membrane vesicles. With endoplasmic reticulum, detergent solubilization of the membranes was required before H-2 antigen could be detected. Nuclear envelope preparations contained little or no demonstrable H-2 activity. These results were confirmed by several techniques including immunoprecipitation of labelled solubilized membrane components with anti-H-2 serum and subsequent analysis in SDS-PAGE. 相似文献
13.
Pei Dong Jessica Flores Kristine Pelton Keith R. Solomon 《Journal of cellular biochemistry》2010,111(5):1367-1374
Cholesterol is essential in establishing most functional animal cell membranes; cells cannot grow or proliferate in the absence of sufficient cholesterol. Consequently, almost every cell, tissue, and animal tightly regulates cholesterol homeostasis, including complex mechanisms of synthesis, transport, uptake, and disposition of cholesterol molecules. We hypothesize that cellular recognition of cholesterol insufficiency causes cell cycle arrest in order to avoid a catastrophic failure in membrane synthesis. Here, we demonstrate using unbiased proteomics and standard biochemistry that cholesterol insufficiency causes upregulation of prohibitin, an inhibitor of cell cycle progression, through activation of a cholesterol‐responsive promoter element. We also demonstrate that prohibitin protects cells from apoptosis caused by cholesterol insufficiency. This is the first study tying cholesterol homeostasis to a specific cell cycle regulator that inhibits apoptosis. J. Cell. Biochem. 111: 1367–1374, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
14.
Edward B. Blanchard Maria L. Peters Christiane Hermann Shannon M. Turner Todd C. Buckley Kristine Barton Mark P. Dentinger 《Applied psychophysiology and biofeedback》1997,22(4):227-245
In order to test for the specific therapeutic effects of thermal biofeedback (TBF) for hand warming on vascular headache (HA),
70 patients with chronic vascular HA were randomly assigned to TBF for hand warming, TBF for hand cooling, TBF for stabilization
of hand temperature, or biofeedback to suppress alpha in the EEG. Patients in each condition initially had high levels of
expectation of therapeutic benefit and found the treatment rationales highly credible. Participants in each condition received
12 treatment sessions on a twice-per-week basis. Based on daily HA diary data gathered for 4 weeks prior to treatment and
4 weeks after treatment, HA Index was significantly (p=.003) reduced as was HA medication consumption. There were no differential
reducations in HA Index or Medication Index among the four conditions. Global self-reports of improvement gathered at the
end of the post-treatment monitoring period also did not differ among the four conditions. We were unable to demonstrate a
specific effect of TBF for hand warming on vascular HA activity. 相似文献
15.
V. Bala Chaudhary Kristine Akland Nancy C. Johnson Matthew A. Bowker 《Restoration Ecology》2020,28(Z2):S115-S126
Biological soil crusts (biocrusts) and arbuscular mycorrhizal (AM) fungi are communities of soil organisms often targeted to assist in the achievement of multiple ecological restoration goals. In drylands, benefits conferred from biocrust and AM fungal inoculation, such as improved native plant establishment and soil stabilization, have primarily been studied separately. However, comparisons between these two types of soil inoculants and investigations into potential synergies between them, particularly at the plant community scale, are needed to inform on‐the‐ground management practices in drylands. We conducted two full‐factorial experiments—one in greenhouse mesocosms and one in field plots—to test the effects of AM fungal inoculation, biocrust inoculation, and their interaction on multiple measures of dryland restoration success. Biocrust inoculation promoted soil stabilization and plant drought tolerance, but had mixed effects on native plant diversity (positive in greenhouse, neutral in field) and productivity (negative in greenhouse, neutral in field). In greenhouse mesocosms, biocrust inoculation reduced plant biomass, which was antagonistic to % root length colonized by AM fungi. Inoculation with native or commercial AM fungi did not influence plant establishment, drought tolerance, or soil stabilization in either study, and few synergistic effects of simultaneous inoculation of AM fungi and biocrusts were observed. These results suggest that, depending on the condition of existing soil communities, inoculation with AM fungi may not be necessary to promote dryland restoration goals, while inoculation with salvaged biocrust inoculation may be beneficial in some contexts. 相似文献
16.
17.
18.
David A Martin Melvin Churchill Luis Felipe Flores-Suarez Mario H Cardiel Daniel Wallace Richard Martin Kristine Phillips Jeffrey L Kaine Hua Dong David Salinger Erin Stevens Chris B Russell James B Chung 《Arthritis research & therapy》2013,15(5):R164
Introduction
The aim of this study was to evaluate the safety, pharmacokinetics, and clinical response of brodalumab (AMG 827), a human, anti-IL-17 receptor A (IL-17RA) monoclonal antibody in subjects with moderate-to-severe rheumatoid arthritis (RA).Methods
This phase Ib, randomized, placebo-controlled, double-blind multiple ascending dose study enrolled subjects with moderate to severe RA (≥6/66 swollen and ≥8/68 tender joints). Subjects were randomized 3:1 to receive brodalumab (50 mg, 140 mg, or 210 mg subcutaneously every two weeks for 6 doses per group; or 420 mg or 700 mg intravenously every 4 weeks for two doses per group) or placebo. Endpoints included incidence of adverse events (AEs) and pharmacokinetics. Exploratory endpoints included pharmacodynamics, and improvements in RA clinical metrics.Results
Forty subjects were randomized to investigational product; one subject discontinued due to worsening of RA (placebo). The study was not designed to assess efficacy. AEs were reported by 70% (7/10) of placebo subjects and 77% (22/30) of brodalumab subjects. Three serious AEs were reported in two subjects; there were no opportunistic infections. Brodalumab treatment resulted in inhibition of IL-17 receptor signaling and receptor occupancy on circulating leukocytes. No treatment effects were observed with individual measures of RA disease activity. On day 85 (week 13) 37% (11/30) of brodalumab subjects and 22% (2/9) of placebo subjects achieved ACR20; 7% (2/30) brodalumab subjects and 11% (1/9) of placebo subjects achieved ACR50; and 0% (0/30) brodalumab subjects and 0% (0/9) of placebo subjects achieved ACR70.Conclusions
Multiple dose administration of brodalumab was tolerated in subjects with active RA. There was no evidence of a clinical response to brodalumab in subjects with RA.Trial registration
ClinicalTrials.gov, NCT00771030相似文献19.
Sandra D. Taylor Kristine K. Barlow‐Stewart Susan A. Treloar Mark Stranger Kellie Chenoweth 《New genetics and society》2013,32(2):225-239
Genetic discrimination, defined as the differential treatment of individuals or their relatives on the basis of actual or presumed genetic differences, is an emerging issue of interest in academic, clinical, social and legal contexts. While its potential significance has been discussed widely, verified empirical data are scarce. Genetic discrimination is a complex phenomenon to describe and investigate, as evidenced by the recent Australian Law Reform Commission inquiry in Australia. The authors research project, which commenced in 2002, aims to document the multiple perspectives and experiences regarding genetic discrimination in Australia and inform future policy development and law reform. Data are being collected from consumers, employers, insurers and the legal system. Attempted verification of alleged accounts of genetic discrimination will be a novel feature of the research. This paper overviews the early stages of the research, including conceptual challenges and their methodological implications. 相似文献
20.
Yanjiao Zhou Hongyu Gao Kathie A Mihindukulasuriya Patricio S La Rosa Kristine M Wylie Tatiana Vishnivetskaya Mircea Podar Barb Warner Phillip I Tarr David E Nelson J Dennis Fortenberry Martin J Holland Sarah E Burr William D Shannon Erica Sodergren George M Weinstock 《Genome biology》2013,14(1):R1