全文获取类型
收费全文 | 2530篇 |
免费 | 200篇 |
国内免费 | 1篇 |
出版年
2023年 | 5篇 |
2022年 | 21篇 |
2021年 | 45篇 |
2020年 | 16篇 |
2019年 | 29篇 |
2018年 | 48篇 |
2017年 | 37篇 |
2016年 | 80篇 |
2015年 | 137篇 |
2014年 | 155篇 |
2013年 | 145篇 |
2012年 | 216篇 |
2011年 | 173篇 |
2010年 | 130篇 |
2009年 | 117篇 |
2008年 | 159篇 |
2007年 | 133篇 |
2006年 | 118篇 |
2005年 | 109篇 |
2004年 | 130篇 |
2003年 | 117篇 |
2002年 | 107篇 |
2001年 | 52篇 |
2000年 | 38篇 |
1999年 | 36篇 |
1998年 | 32篇 |
1997年 | 19篇 |
1996年 | 23篇 |
1995年 | 13篇 |
1994年 | 20篇 |
1993年 | 14篇 |
1992年 | 21篇 |
1991年 | 14篇 |
1990年 | 28篇 |
1989年 | 18篇 |
1988年 | 7篇 |
1987年 | 15篇 |
1986年 | 20篇 |
1985年 | 18篇 |
1984年 | 11篇 |
1983年 | 13篇 |
1982年 | 7篇 |
1981年 | 9篇 |
1980年 | 9篇 |
1979年 | 7篇 |
1978年 | 7篇 |
1976年 | 5篇 |
1975年 | 7篇 |
1974年 | 7篇 |
1973年 | 9篇 |
排序方式: 共有2731条查询结果,搜索用时 15 毫秒
991.
Rüttinger C Bergmann M Fink L Pesch S Seitz K Trautmann A Steger K Konrad L Brehm R 《Histochemistry and cell biology》2008,130(3):537-548
In human testis, gap junctions containing connexin(Cx)43 are located within the seminiferous epithelium between Sertoli cells and between Sertoli and germ cells. Cx43 is known to play a role in the differentiation and proliferation of these cell types. It can further be associated with human seminoma development. The dog has been proposed as a model for studies of the male reproductive system, because of the frequent occurrence of testicular neoplasms. Thus, we investigated Cx43-mRNA and -protein expression in testes of normal prepubertal dogs, adult dogs, and in canine testicular tumors. Sertoli cells in prepubertal cords express Cx43 mRNA, but do synthesize only less Cx43 protein. Within the seminiferous tubules, Cx43 mRNA was detected in Sertoli cells, spermatogonia, and spermatocytes. Cx43 protein was mainly present in the basal compartment. In canine testicular tumors Cx43 mRNA was detectable in both seminoma and neoplastic Sertoli cells, whereas Cx43 protein was only found in neoplastic Sertoli cells. Our data indicate that Cx43 is regulated differentially in testicular tumors and that alterations of Cx43 expression may be involved in the pathogenesis of canine testicular malignancies. This study represents the first morphological work on the spatiotemporal expression pattern of Cx43 in normal and neoplastic canine testis. 相似文献
992.
Caroline Trebbien Gottlieb Line Elnif Thomsen Hanne Ingmer Per Holse Mygind Hans-Henrik Kristensen Lone Gram 《BMC microbiology》2008,8(1):205
Background
Host defense peptides (HDPs), or antimicrobial peptides (AMPs), are important components of the innate immune system that bacterial pathogens must overcome to establish an infection and HDPs have been suggested as novel antimicrobial therapeutics in treatment of infectious diseases. Hence it is important to determine the natural variation in susceptibility to HDPs to ensure a successful use in clinical treatment regimes. 相似文献993.
Background
Cyanopeptolins are nonribosomally produced heptapetides showing a highly variable composition. The cyanopeptolin synthetase operon has previously been investigated in three strains from the genera Microcystis, Planktothrix and Anabaena. Cyanopeptolins are displaying protease inhibitor activity, but the biological function(s) is (are) unknown. Cyanopeptolin gene cluster variability and biological functions of the peptide variants are likely to be interconnected. 相似文献994.
During type 1 diabetes, most beta cells die by immune processes. However, the precise fate and characteristics of beta cells
and islet autoimmunity after onset are unclear. Here, the extent of beta cell survival was determined in the non-obese diabetic
(NOD) mouse during increasing duration of disease and correlated with insulitis. Pancreata from female NOD mice at diagnosis
and at 1, 2, 3 and 4 weeks thereafter were analysed immunohistochemically for insulin, glucagon and somatostatin cells and
glucose transporter-2 (glut2) and correlated with the degree of insulitis and islet immune cell phenotypes. Insulitis, although
variable, persisted after diabetes and declined with increasing duration of disease. During this period, beta cells also declined
sharply whereas glucagon and somatostatin cells increased, with occasional islet cells co-expressing insulin and glucagon.
Glut2 was absent in insulin-containing cells from 1 week onwards. CD4 and CD8 T cells and macrophages persisted until 4 weeks,
in islets with residual beta cells or extensive insulitis. We conclude that after diabetes onset, some beta cells survive
for extended periods, with continuing autoimmunity and expansion of glucagon and somatostatin cells. The absence of glut2
in several insulin-positive cells suggests that some beta cells may be unresponsive to glucose. 相似文献
995.
Zwerdling A Delpino MV Barrionuevo P Cassataro J Pasquevich KA García Samartino C Fossati CA Giambartolomei GH 《Microbes and infection / Institut Pasteur》2008,10(12-13):1346-1354
Infection with Brucella abortus induces a pro-inflammatory response that drives T cell responses toward a Th1 profile. The mechanism by which this bacterium triggers this response is unknown. Dendritic cells (DC) are crucial mediators at the host-pathogen interface and are potent Th1-inducing antigen-presenting cells. Thus, we examined the mechanism whereby B. abortus stimulate human DC maturation. B. abortus-infected DC increased the expression of CD86, CD80, CCR7, CD83, MHCII, MHCI and CD40 and induced the production of TNF-alpha, IL-6, IL-10 and IL-12. Both phenomena were not dependent on bacterial viability since they were also induced by heat-killed B. abortus (HKBA). B. abortus LPS was unable to induce markers up-regulation or cytokine production. We next investigated the capacity of the outer membrane protein 19 (Omp19) as a B. abortus lipoprotein model to induce DC maturation. Lipidated Omp19 (L-Omp19), but not its unlipidated form, increased the expression of cell surface markers and the secretion of cytokines. L-Omp19-matured DC also have decreased endocytic activity and displayed enhanced T cell stimulatory activity in a MLR. Pre-incubation of DC with anti-TLR2 mAb blocked L-Omp19-mediated cytokine production. These results demonstrate that B. abortus lipoproteins can stimulate DC maturation providing a mechanism by which these bacteria generate a Th1-type immune response. 相似文献
996.
Genome sequencing and analysis of the biomass-degrading fungus Trichoderma reesei (syn. Hypocrea jecorina) 总被引:1,自引:0,他引:1
Martinez D Berka RM Henrissat B Saloheimo M Arvas M Baker SE Chapman J Chertkov O Coutinho PM Cullen D Danchin EG Grigoriev IV Harris P Jackson M Kubicek CP Han CS Ho I Larrondo LF de Leon AL Magnuson JK Merino S Misra M Nelson B Putnam N Robbertse B Salamov AA Schmoll M Terry A Thayer N Westerholm-Parvinen A Schoch CL Yao J Barabote R Barbote R Nelson MA Detter C Bruce D Kuske CR Xie G Richardson P Rokhsar DS Lucas SM Rubin EM Dunn-Coleman N Ward M Brettin TS 《Nature biotechnology》2008,26(5):553-560
Trichoderma reesei is the main industrial source of cellulases and hemicellulases used to depolymerize biomass to simple sugars that are converted to chemical intermediates and biofuels, such as ethanol. We assembled 89 scaffolds (sets of ordered and oriented contigs) to generate 34 Mbp of nearly contiguous T. reesei genome sequence comprising 9,129 predicted gene models. Unexpectedly, considering the industrial utility and effectiveness of the carbohydrate-active enzymes of T. reesei, its genome encodes fewer cellulases and hemicellulases than any other sequenced fungus able to hydrolyze plant cell wall polysaccharides. Many T. reesei genes encoding carbohydrate-active enzymes are distributed nonrandomly in clusters that lie between regions of synteny with other Sordariomycetes. Numerous genes encoding biosynthetic pathways for secondary metabolites may promote survival of T. reesei in its competitive soil habitat, but genome analysis provided little mechanistic insight into its extraordinary capacity for protein secretion. Our analysis, coupled with the genome sequence data, provides a roadmap for constructing enhanced T. reesei strains for industrial applications such as biofuel production. 相似文献
997.
Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2 总被引:3,自引:0,他引:3
Huangfu D Osafune K Maehr R Guo W Eijkelenboom A Chen S Muhlestein W Melton DA 《Nature biotechnology》2008,26(11):1269-1275
Ectopic expression of defined sets of genetic factors can reprogram somatic cells to induced pluripotent stem (iPS) cells that closely resemble embryonic stem (ES) cells. The low efficiency with which iPS cells are derived hinders studies on the molecular mechanism of reprogramming, and integration of viral transgenes, in particular the oncogenes c-Myc and Klf4, may handicap this method for human therapeutic applications. Here we report that valproic acid (VPA), a histone deacetylase inhibitor, enables reprogramming of primary human fibroblasts with only two factors, Oct4 and Sox2, without the need for the oncogenes c-Myc or Klf4. The two factor-induced human iPS cells resemble human ES cells in pluripotency, global gene expression profiles and epigenetic states. These results support the possibility of reprogramming through purely chemical means, which would make therapeutic use of reprogrammed cells safer and more practical. 相似文献
998.
999.
1000.
Dürauer A Berger E Zandian M Mersich C Schuster M Loibner H Jungbauer A 《Journal of biochemical and biophysical methods》2008,70(6):1109-1115
Even though an immunogenic formulation of the murine monoclonal anti-EpCAM (epithelian cell adhesion molecule) antibody Mab 17-1A, has been shown to evoke a strong humoral immune response in both, monkey studies and early clinical trials, conventional anti-EpCAM ELISA could not identify anti-EpCAM immune response in relation to treatment with Mab17-1A. In contrast, usage of cellulose membranes prepared by SPOT technology presenting overlapping EpCAM peptides allowed the unequivocal determination of EpCAM related antibodies present in monkeys sera after immunization with IGN101. Based on such contradictory results, it was of high interest to compare obtained data to a different method for better assessment of their possible interpretation. Therefore, in the present studies, some EpCAM peptides, determined as reactive by binding of IgG isolated from sera of treated monkeys on membranes prepared by SPOT technology, were represented on yeast surface using the pYD1 yeast display vector system. Binding of biotinylated IgG from sera was detected with streptavidin–FITC and quantity of binding was determined by FACS measurement. Though using this completely different method, experiments with pre-immune and immune sera of four monkeys exemplarily are comparable to the results obtained by analysis with synthetic peptide arrays. 相似文献