全文获取类型
收费全文 | 10668篇 |
免费 | 802篇 |
国内免费 | 594篇 |
专业分类
12064篇 |
出版年
2024年 | 20篇 |
2023年 | 139篇 |
2022年 | 273篇 |
2021年 | 429篇 |
2020年 | 295篇 |
2019年 | 345篇 |
2018年 | 360篇 |
2017年 | 291篇 |
2016年 | 479篇 |
2015年 | 629篇 |
2014年 | 747篇 |
2013年 | 817篇 |
2012年 | 979篇 |
2011年 | 909篇 |
2010年 | 561篇 |
2009年 | 489篇 |
2008年 | 582篇 |
2007年 | 539篇 |
2006年 | 461篇 |
2005年 | 414篇 |
2004年 | 361篇 |
2003年 | 346篇 |
2002年 | 315篇 |
2001年 | 138篇 |
2000年 | 136篇 |
1999年 | 116篇 |
1998年 | 84篇 |
1997年 | 82篇 |
1996年 | 66篇 |
1995年 | 56篇 |
1994年 | 63篇 |
1993年 | 49篇 |
1992年 | 62篇 |
1991年 | 55篇 |
1990年 | 51篇 |
1989年 | 37篇 |
1988年 | 26篇 |
1987年 | 18篇 |
1986年 | 32篇 |
1985年 | 22篇 |
1984年 | 29篇 |
1983年 | 10篇 |
1982年 | 14篇 |
1981年 | 14篇 |
1980年 | 13篇 |
1979年 | 8篇 |
1978年 | 8篇 |
1977年 | 12篇 |
1976年 | 11篇 |
1975年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
OBJECTIVES: The study investigated the association of TNFR1 gene polymorphism with early recurrent spontaneous miscarriage (ERSM) in Chinese women, and soluble TNFR1 (sTNFR1) expression in ERSM women. STUDY DESIGN: Two single nucleotide polymorphisms (SNPs) located at -383 (AGA to AGC) in the promoter region and +36 (CCA to CCG) in exon 1 of TNFR1 were investigated in 188 non-pregnant ERSM Chinese women. The serum sTNFR1 was measured by the ELISA method. RESULTS: Both SNPs were not associated with ERSM. The non-pregnant ERSM women had significantly higher levels of serum sTNFR1, compared with the non-pregnant, normal women (1.84+/-0.54 ng/ml versus 1.62+/-0.38 ng/ml; t=-2.053; p<0.05). CONCLUSIONS: The data do not provide evidence that TNFR1 gene polymorphism is etiologically important for ERSM in Chinese women. But, a significantly raised sTNFR1 level in non-pregnant ERSM women was recorded compared to women with normal pregnancies. The result suggests that pregnancy failure is associated with an increase of sTNFR1. 相似文献
992.
Assembling millions of short DNA sequences using SSAKE 总被引:7,自引:0,他引:7
Novel DNA sequencing technologies with the potential for up to three orders magnitude more sequence throughput than conventional Sanger sequencing are emerging. The instrument now available from Solexa Ltd, produces millions of short DNA sequences of 25 nt each. Due to ubiquitous repeats in large genomes and the inability of short sequences to uniquely and unambiguously characterize them, the short read length limits applicability for de novo sequencing. However, given the sequencing depth and the throughput of this instrument, stringent assembly of highly identical sequences can be achieved. We describe SSAKE, a tool for aggressively assembling millions of short nucleotide sequences by progressively searching through a prefix tree for the longest possible overlap between any two sequences. SSAKE is designed to help leverage the information from short sequence reads by stringently assembling them into contiguous sequences that can be used to characterize novel sequencing targets. Availability: http://www.bcgsc.ca/bioinfo/software/ssake. 相似文献
993.
Ca2+/calmodulin-dependent protein kinase kinase is involved in AMP-activated protein kinase activation by alpha-lipoic acid in C2C12 myotubes 总被引:1,自引:0,他引:1
Shen QW Zhu MJ Tong J Ren J Du M 《American journal of physiology. Cell physiology》2007,293(4):C1395-C1403
alpha-Lipoic acid (ALA) widely exists in foods and is an antidiabetic agent. ALA stimulates glucose uptake and increases insulin sensitivity by the activation of AMP-activated protein kinase (AMPK) in skeletal muscle, but the underlying mechanism for AMPK activation is unknown. Here, we investigated the mechanism through which ALA activates AMPK in C2C12 myotubes. Incubation of C2C12 myotubes with 200 and 500 microM ALA increased the activity and phosphorylation of the AMPK alpha-subunit at Thr(172). Phosphorylation of the AMPK substrate, acetyl CoA carboxylase (ACC), at Ser(79) was also increased. No difference in ATP, AMP, and the calculated AMP-to-ATP ratio was observed among the different treatment groups. Since the upstream AMPK kinase, LKB1, requires an alteration of the AMP-to-ATP ratio to activate AMPK, this data showed that LKB1 might not be involved in the activation of AMPK induced by ALA. Treatment of ALA increased the intracellular Ca(2+) concentration measured by fura-2 fluorescent microscopy (P < 0.05), showing that ALA may activate AMPK through enhancing Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK) signaling. Indeed, chelation of intracellular free Ca(2+) by loading cells with 25 microM BAPTA-AM for 30 min abolished the ALA-induced activation of AMPK and, in turn, phosphorylation of ACC at Ser(79). Furthermore, inhibition of CaMKK using its selective inhibitor, STO-609, abolished ALA-stimulated AMPK activation, with an accompanied reduction of ACC phosphorylation at Ser(79). In addition, ALA treatment increased the association of AMPK with CaMKK. To further show the role of CaMKK in AMPK activation, short interfering RNA was used to silence CaMKK, which abolished the ALA-induced AMPK activation. These data show that CaMKK is the kinase responsible for ALA-induced AMPK activation in C2C12 myotubes. 相似文献
994.
Floral morphogenesis and the development of Cercidiphyllum japonicum Sieb.et Zucc.were observed by scanning electronmicroscopy(SEM).The results showed that the pistillate inflorescences were congested spikes with the flowers arrangedopposite.Great differences between the so-called"bract"and the vegetative leaf were observed both in morphogenesis andmorphology.In morphogenesis,the"bract"primordium is crescent-shaped,truncated at the apex and not conduplicate,has no stipule primordium at the base but does have some inconspicuous teeth in the margin that are not glandular.Theleaf primordium is triangular,cycloidal at the apex,conduplicate,has two stipule primordia at the base,has one gland-toothat the apex occurring at first and some gland-teeth in the margin that occur later.In morphology,the"bract"is also differentto the vegetative leaf in some characteristics that were also illustrated in the present paper.Based on the hypothesis thatthe bract is more similar to the vegetative leaf than the tepal,we considered that the so-called"bract"of C.japonicum mightbe the tepal of the pistillate flower in morphological nature.Therefore,each pistillate flower contains a tepal and a carpel.We did not find any trace of other floral organs in the morphogenesis of the pistillate flower.Therefore we consideredthat the unicarpellate status of extant Cercidiphyllum might be to highly reduce and advance characteristics that make theextant Cercidiphyllum isolated from both fossil Cercidiphyllum-like plants and its extant affinities. 相似文献
995.
996.
Interleukin-17F (IL-17F), together with interleukin-17A (IL-17 or IL-17A), is a marker of T(H)17 cells, a new lineage of effector CD4(+) T cells to contribute to pathogenesis of a growing list of autoimmune and inflammatory diseases, such as experimental autoimmune encephalitis (EAE) and collagen-induced arthritis (CIA). IL-17F, similar to IL-17A, was reported to employ interleukin-17 receptor (IL-17R or IL-17RA) for signaling but the downstream cascades remain largely elusive. Here we report that TRAF6 interacts with IL-17R and mediates ubiquitination of the receptor. We observed that IL-17F and IL-17A could induce IL-17R ubiquitination and DN-TRAF6, a dominant-negative mutant, could block IL-17F- but not IL-17A-triggered ubiquitination of IL-17R. Moreover, we showed that the ubiquitination of IL-17R was positively correlated with the downstream signaling, as evaluated by a luciferase reporter driven by a putative native promoter of 24p3, an IL-17 targeted gene. Our results indicate that ubiquitination of IL-17R mediated by TRAF6 plays a critical role in IL-17F signaling. This study, for the first time, reveals a possible molecular mechanism that the initiation of the IL-17F/IL-17R signaling pathway requires the receptor ubiquitination by TRAF6. 相似文献
997.
Changes in forest cover in China during the Holocene 总被引:3,自引:0,他引:3
Guoyu Ren 《Vegetation History and Archaeobotany》2007,16(2-3):119-126
Pollen map data at 2000-year intervals are used to reconstruct changes in Holocene forest cover in China north of the Yangtze
River. In almost all regions, the early Holocene from 10 ka b.p. to 6 ka b.p. is characterised by an increase in forest cover although there was a reversal to lower forest cover at 8 ka b.p. in the eastern monsoon regions. A maximum of forest cover was reached at 6 ka b.p. in all regions except for Northeast China where forest cover peaked in the late Holocene. All regions except for Northeast
China experienced a marked decline in forest cover after 6 ka b.p. Since 6 ka b.p., forest cover has decreased by about 92% in the middle and lower reaches of the Yellow River, 64% in the easternmost part
of the Qinghai-Tibet Plateau and 37% between the Yangtze River and the Huaihe River. In contrast, forest cover in Northeast
China increased significantly from 6 ka b.p., but has declined between 2 ka b.p. and the present. Changes in forest cover prior to 6 ka b.p. were probably caused by climate, but the evident drop in forest cover since that time in most regions may have been induced
predominantly by human activities. 相似文献
998.
Han C Smolen JS Kavanaugh A van der Heijde D Braun J Westhovens R Zhao N Rahman MU Baker D Bala M 《Arthritis research & therapy》2007,9(5):R103
In this study, we compare the health-related quality of life (HRQoL) of patients with moderate-to-severe rheumatoid arthritis
(RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), and study the effect of treatment with infliximab on the
HRQoL of patients with these diseases. Short Form Health Survey-36 (SF-36) data from the placebo-controlled phases of 4 studies
of infliximab in patients with inflammatory rheumatic diseases (n = 1990) were evaluated. Data came from the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) (n = 428), the Safety Trial for Rheumatoid Arthritis with REMICADE Therapy (START) (n = 1083), the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) (n = 279), and the Infliximab Multinational Psoriatic Arthritis Clinical Trial II (IMPACT II) (n = 200). SF-36 assessments were made at weeks 0, 10, 30, and 54 in ATTRACT, weeks 0, 6, and 22 in START, weeks 0, 12, and
24 in ASSERT, and weeks 0 and 14 in IMPACT II. All patient populations had significantly impaired physical aspects of HRQoL
at baseline relative to the general population of the United States, and the magnitude of impairment was similar across the
diseases. Mean baseline physical component summary scores were 29 in the RA cohort, 32 in the PsA cohort, and 29 in the AS
cohort. In all 3 diseases, patients who received infliximab showed significant improvement in physical component summary scores
compared with those who received placebo. The magnitude of the difference of improvement (effect size, 95%CI) between infliximab
and placebo groups was similar in the AS (10.1, 9.2–11.0), PsA (8.6, 7.8–9.4), and RA (10.1, 9.2–11.0) cohorts. Patients with
RA and those with PsA treated with infliximab also showed greater improvement in the mental component summary score than those
in the placebo group with an effect size of 4.6 (4.2–5.1) in RA and 2.7 (2.4–3.1) in PsA. Patients in large randomized controlled
studies of infliximab in RA, PsA, and AS had similar impairment in physical aspects of HRQoL at baseline and showed significantly
greater improvement in HRQoL after treatment with infliximab. 相似文献
999.
Zheng ZH Dong YS Zhang H Lu XH Ren X Zhao G He JG Si SY 《Journal of enzyme inhibition and medicinal chemistry》2007,22(1):43-49
A high throughput screening was carried out in order to search for inhibitors of acetylcholinesterase (AChE) from microorganism metabolites. An actinomycete strain was found to produce active compounds named N98-1272 A, B and C with IC50 of 15.0, 11.5, 12.5 microM, respectively. Structural studies revealed that the three compounds are identical to the known antibiotics, Manumycin C, B and A. Kinetic analyses showed that N98-1272 C (Manumycin A) acted as a reversible noncompetitive inhibitor of acetylcholinesterase, with a Ki value of 7.2 microM. The cyclohexenone epoxide part of the structure plays a crucial role in the inhibitory activity against AChE. Compared with Tacrine, N98-1272 A, B, and C exhibit much better selectivity toward AChE over BuChE. 相似文献
1000.
Tripeptidyl peptidase II (TPPII) is a multifunctional and evolutionarily conserved protease. In the mammalian hypothalamus, TPPII has a proposed anti-satiety role affected by degradation of the satiety hormone cholecystokinin 8. Here, we show that TPPII also regulates the metabolic homoeostasis of Caenorhabditis elegans; TPPII RNA interference (RNAi) decreases worm fat stores. However, this occurs independently of feeding behaviour and seems to be a function within fat-storing tissues. In mammalian cell culture, TPPII stimulates adipogenesis and TPPII RNAi blocks adipogenesis. The pro-adipogenic action of TPPII seems to be independent of protease function, as catalytically inactive TPPII also increases adipogenesis. Mice that were homozygous for an insertion in the Tpp2 locus were embryonic lethal. However, Tpp2 heterozygous mutants were lean compared with wild-type littermates, although food intake was normal. These findings indicate that TPPII has central and peripheral roles in regulating metabolism and that TPPII actions in fat-storing tissues might be an ancient function carried out in a protease-independent manner. 相似文献