全文获取类型
收费全文 | 3510篇 |
免费 | 376篇 |
出版年
2021年 | 45篇 |
2018年 | 35篇 |
2017年 | 36篇 |
2016年 | 58篇 |
2015年 | 107篇 |
2014年 | 90篇 |
2013年 | 129篇 |
2012年 | 141篇 |
2011年 | 169篇 |
2010年 | 87篇 |
2009年 | 94篇 |
2008年 | 108篇 |
2007年 | 116篇 |
2006年 | 115篇 |
2005年 | 106篇 |
2004年 | 128篇 |
2003年 | 90篇 |
2002年 | 102篇 |
2001年 | 82篇 |
2000年 | 105篇 |
1999年 | 83篇 |
1998年 | 61篇 |
1997年 | 56篇 |
1996年 | 54篇 |
1995年 | 45篇 |
1994年 | 36篇 |
1993年 | 51篇 |
1992年 | 83篇 |
1991年 | 68篇 |
1990年 | 79篇 |
1989年 | 59篇 |
1988年 | 62篇 |
1987年 | 82篇 |
1986年 | 61篇 |
1985年 | 66篇 |
1984年 | 63篇 |
1983年 | 49篇 |
1982年 | 56篇 |
1981年 | 40篇 |
1980年 | 31篇 |
1979年 | 47篇 |
1978年 | 29篇 |
1977年 | 32篇 |
1976年 | 48篇 |
1975年 | 41篇 |
1974年 | 45篇 |
1973年 | 36篇 |
1972年 | 34篇 |
1971年 | 37篇 |
1968年 | 29篇 |
排序方式: 共有3886条查询结果,搜索用时 62 毫秒
991.
Oliver Löwenstein Petra Leyendecker Eberhard A Lux Mark Blagden Karen H Simpson Michael Hopp Björn Bosse Karen Reimer 《BMC clinical pharmacology》2010,10(1):12
Background
Two randomised 12-week, double-blind, parallel-group, multicenter studies comparing oxycodone PR/naloxone PR and oxycodone PR alone on symptoms of opioid-induced bowel dysfunction in patients with moderate/severe non-malignant pain have been conducted. 相似文献992.
St��phanie Ramboarina James A. Garnett Meixian Zhou Yuebin Li Zhixiang Peng Jonathan D. Taylor Wei-chao Lee Andrew Bodey James W. Murray Yilmaz Alguel Julien Bergeron Benjamin Bardiaux Elizabeth Sawyer Rivka Isaacson Camille Tagliaferri Ernesto Cota Michael Nilges Peter Simpson Teresa Ruiz Hui Wu Stephen Matthews 《The Journal of biological chemistry》2010,285(42):32446-32457
The serine-rich repeat family of fimbriae play important roles in the pathogenesis of streptococci and staphylococci. Despite recent attention, their finer structural details and precise adhesion mechanisms have yet to be determined. Fap1 (Fimbriae-associated protein 1) is the major structural subunit of serine-rich repeat fimbriae from Streptococcus parasanguinis and plays an essential role in fimbrial biogenesis, adhesion, and the early stages of dental plaque formation. Combining multidisciplinary, high resolution structural studies with biological assays, we provide new structural insight into adhesion by Fap1. We propose a model in which the serine-rich repeats of Fap1 subunits form an extended structure that projects the N-terminal globular domains away from the bacterial surface for adhesion to the salivary pellicle. We also uncover a novel pH-dependent conformational change that modulates adhesion and likely plays a role in survival in acidic environments. 相似文献
993.
The diploid rainbow trout Oncorhynchus mykiss reached sexual maturity 3 years after hatching and its oogenesis underwent four stages, which were oogonia, primary oocyte, secondary oocyte and egg. Reproductive development and hormone changes of 4 to 35 month‐old female O. mykiss were investigated using histological and radioimmunoassay methods in order to provide a theoretical and practical basis for the use of triploid female O. mykiss. The oogonium of the triploid female could develop into the oocytes of the prophase with abortion occurring later; the oogonium was surrounded by stroma cells to form the oogonium cluster and the gonads showed a virilescent tendency when the oogonium clusters were gradually replaced by spermatogenic‐like cytocysts. After 13 months, amounts of gonadotropic hormone (GtH‐I, GtH‐II) and oestradiol (17β‐E2) in triploid females were lower than in diploid fish at corresponding time periods, but the amounts of testosterone (T) increased consistently after 21 months and were more than in diploid fish in the corresponding time periods (P > 0·05). The infertility of triploid females resulted from meiosis failure, which caused developmental abortion of oocytes and oogonium formed cytocysts before the prophase oocytes. The cytocyst formation was due to the lack of the normal interaction of ovum and follicular cells, the development of follicular cells producing steroids were inhibited, the arylate path from T to 17β‐E2 was interrupted, concentration of 17β‐E2 decreased and concentration of T increased in the blood, the content of vitellogenin (Vg) decreased in the liver with a low 17β‐E2 and high T caused to ovaries to show a tendency to be virilescent. 相似文献
994.
Darron A. Cullen Gregory A. Sword Tim Dodgson Stephen J. Simpson 《Journal of insect physiology》2010,56(8):937-128
Density-dependent phase polyphenism is a defining characteristic of the paraphyletic group of acridid grasshoppers known as locusts. The cues and mechanisms associated with crowding that induce behavioural gregarization are best understood in the desert locust, Schistocerca gregaria, and involve a combination of sensory inputs from the head (visual and olfactory) and mechanostimulation of the hind legs, acting via a transient increase in serotonin in the thoracic ganglia. Since behavioural gregarization has apparently arisen independently multiple times within the Acrididae, the important question arises as to whether the same mechanisms have been recruited each time. Here we explored the roles of visual, olfactory and tactile stimulation in the induction of behavioural gregarization in the Australian plague locust, Chortoicetes terminifera. We show that the primary gregarizing input is tactile stimulation of the antennae, with no evidence for an effect of visual and olfactory stimulation or tactile stimulation of the hind legs. Our results show that convergent behavioural responses to crowding have evolved employing different sites of sensory input in the Australian plague locust and the desert locust. 相似文献
995.
Otavia L. Caballero Qi Zhao Donata Rimoldi Brian J. Stevenson Suzanne Svobodová Sylvie Devalle Ute F. R?hrig Anna Pagotto Olivier Michielin Daniel Speiser Jedd D. Wolchok Cailian Liu Tanja Pejovic Kunle Odunsi Francis Brasseur Benoit J. Van den Eynde Lloyd J. Old Xin Lu Jonathan Cebon Robert L. Strausberg Andrew J. Simpson 《PloS one》2010,5(9)
Background
Cancer/testis (CT) genes are expressed only in the germ line and certain tumors and are most frequently located on the X-chromosome (the CT-X genes). Amongst the best studied CT-X genes are those encoding several MAGE protein families. The function of MAGE proteins is not well understood, but several have been shown to potentially influence the tumorigenic phenotype.Methodology/Principal Findings
We undertook a mutational analysis of coding regions of four CT-X MAGE genes, MAGEA1, MAGEA4, MAGEC1, MAGEC2 and the ubiquitously expressed MAGEE1 in human melanoma samples. We first examined cell lines established from tumors and matching blood samples from 27 melanoma patients. We found that melanoma cell lines from 37% of patients contained at least one mutated MAGE gene. The frequency of mutations in the coding regions of individual MAGE genes varied from 3.7% for MAGEA1 and MAGEA4 to 14.8% for MAGEC2. We also examined 111 fresh melanoma samples collected from 86 patients. In this case, samples from 32% of the patients exhibited mutations in one or more MAGE genes with the frequency of mutations in individual MAGE genes ranging from 6% in MAGEA1 to 16% in MAGEC1.Significance
These results demonstrate for the first time that the MAGE gene family is frequently mutated in melanoma. 相似文献996.
997.
David C. Simpson Edward Kabyemela Atis Muehlenbachs Yuko Ogata Theonest K. Mutabingwa Patrick E. Duffy Michal Fried 《PloS one》2010,5(1)
Background
Plasmodium falciparum placental malaria (PM) contributes to 10,000 maternal deaths due to severe anemia (SA) each year in Africa, primarily among primigravid women who are most susceptible. Increased levels of proinflammatory cytokines like TNF-α are associated with maternal anemia in first time mothers but not in other women. Here we aimed to identify additional changes in the plasma proteome associated with pregnancy malaria that may contribute to the development of malaria-related maternal anemia.Principal Findings
A semi-quantitative mass spectrometry approach was used to compare the relative abundance of plasma proteins in anemic versus non-anemic women with PM. Levels of 24 proteins differed significantly between anemic and non-anemic primigravidae, including several lipid metabolism proteins and molecular transport proteins involved in the acute phase response signaling network. These differences were not observed in multigravid women who enjoy specific immunity that protect them from PM. In a confirmatory study of a larger cohort of primigravid women, levels of the lipid metabolism protein Apolipoprotein (Apo)-AI were significantly lower in PM+ women with SA.Conclusions
Apo-AI levels are significantly lower in severely anemic primigravidae with PM, and ApoA1 levels positively correlate with hemoglobin levels in primigravid but not multigravid women. Apo-AI is known to have anti-inflammatory effects, and thus Apo-AI reductions may contribute to the inflammatory processes that result in SA. 相似文献998.
Clarizia AD Bastos-Rodrigues L Pena HB Anacleto C Rossi B Soares FA Lopes A Rocha JC Caballero O Camargo A Simpson AJ Pena SD 《Genetics and molecular research : GMR》2006,5(2):315-322
The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with the expression of a thermolabile enzyme with decreased activity that influences the pool of methyl-donor molecules. Several studies have reported an association between C677T polymorphism and susceptibility to colorectal cancer (CRC). Considering that methylation abnormalities appear to be important for the pathogenesis of CRC, we examined the correlation between the genotype of the MTHFR C677T polymorphism, hypermethylation of the promoter region of five relevant genes (DAPK, MGMT, hMLH1, p16(INK4a), and p14(ARF)), and microsatellite instability, in 106 patients with primary CRCs in Brazil. We did not find significant differences in the genotypic frequencies of the MTHFR C677T polymorphism when one or more loci were hypermethylated. However, we did find a significant excess of 677TT individuals among patients with CRC who had microsatellite instability. This strong association was independent of the methylation status of hMLH1 and of the biogeographical genomic ancestry of the patients. Although the mechanism responsible for the link between the C677T polymorphism and microsatellite instability was not apparent, this finding may provide a clue towards a better understanding of the pathogenesis of microsatellite instability in human colorectal cancer. 相似文献
999.
JC Biro 《Theoretical biology & medical modelling》2006,3(1):15-12
Background
Prediction of protein folding and specific interactions from only the sequence (ab initio) is a major challenge in bioinformatics. It is believed that such prediction will prove possible if Anfinsen's thermodynamic principle is correct for all kinds of proteins, and all the information necessary to form a concrete 3D structure is indeed present in the sequence. 相似文献1000.
Daniel J Jackson Carmel McDougall Kathryn Green Fiona Simpson Gert Wörheide Bernard M Degnan 《BMC biology》2006,4(1):40-10