首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   3411篇
  免费   217篇
  2022年   16篇
  2021年   33篇
  2019年   28篇
  2018年   38篇
  2017年   35篇
  2016年   78篇
  2015年   92篇
  2014年   130篇
  2013年   133篇
  2012年   224篇
  2011年   246篇
  2010年   187篇
  2009年   140篇
  2008年   187篇
  2007年   187篇
  2006年   166篇
  2005年   173篇
  2004年   151篇
  2003年   175篇
  2002年   158篇
  2001年   39篇
  2000年   27篇
  1999年   58篇
  1998年   58篇
  1997年   45篇
  1996年   60篇
  1995年   40篇
  1994年   43篇
  1993年   33篇
  1992年   51篇
  1991年   30篇
  1990年   42篇
  1989年   28篇
  1988年   21篇
  1987年   16篇
  1986年   14篇
  1985年   18篇
  1984年   27篇
  1983年   23篇
  1982年   30篇
  1981年   32篇
  1980年   21篇
  1979年   34篇
  1978年   19篇
  1977年   19篇
  1976年   18篇
  1971年   15篇
  1970年   16篇
  1969年   13篇
  1967年   14篇
排序方式: 共有3628条查询结果,搜索用时 31 毫秒
131.
The prothoracic glands of the last instar of Galleria mellonella undergo characteristic alterations of their cellular fine structure closely related to cellular activity. During progressive secretory activity of the gland cells there are extensive plasmalemmal infoldings and formation of a pronounced lacunar system. Mitochondria of the active cell phase are characterized by a specific increase in size and paler colour of the matrix. In contrast to the alterations, nuclei, ER and Golgi cisterns do not undergo any submicroscopic changes during the different phases of cellular activity. The relationship between the substructural phenomena and the specific phases of cellular activity are discussed.  相似文献   
132.
Decision rules of reciprocity include ‘I help those who helped me’ (direct reciprocity) and ‘I help those who have helped others’ (indirect reciprocity), i.e. I help those who have a reputation to care for others. A person''s reputation is a score that members of a social group update whenever they see the person interacting or hear at best multiple gossip about the person''s social interactions. Reputation is the current standing the person has gained from previous investments or refusal of investments in helping others. Is he a good guy, can I trust him or should I better avoid him as a social partner? A good reputation pays off by attracting help from others, even from strangers or members from another group, if the recipient''s reputation is known. Any costly investment in others, i.e. direct help, donations to charity, investment in averting climate change, etc. increases a person''s reputation. I shall argue and illustrate with examples that a person''s known reputation functions like money that can be used whenever the person needs help. Whenever possible I will present tests of predictions of evolutionary theory, i.e. fitness maximizing strategies, mostly by economic experiments with humans.  相似文献   
133.
134.
The genome‐wide association studies (GWASs) are essential to determine the genetic bases of either ecological or economic phenotypic variation across individuals within populations of the model and nonmodel organisms. For this research question, the GWAS replication testing different parameters and models to validate the results'' reproducibility is common. However, straightforward methodologies that manage both replication and tetraploid data are still missing. To solve this problem, we designed the MultiGWAS, a tool that does GWAS for diploid and tetraploid organisms by executing in parallel four software packages, two designed for polyploid data (GWASpoly and SHEsis) and two designed for diploid data (GAPIT and TASSEL). MultiGWAS has several advantages. It runs either in the command line or in a graphical interface; it manages different genotype formats, including VCF. Moreover, it allows control for population structure, relatedness, and several quality control checks on genotype data. Besides, MultiGWAS can test for additive and dominant gene action models, and, through a proprietary scoring function, select the best model to report its associations. Finally, it generates several reports that facilitate identifying false associations from both the significant and the best‐ranked association Single Nucleotide Polymorphisms (SNPs) among the four software packages. We tested MultiGWAS with public tetraploid potato data for tuber shape and several simulated data under both additive and dominant models. These tests demonstrated that MultiGWAS is better at detecting reliable associations than using each of the four software packages individually. Moreover, the parallel analysis of polyploid and diploid software that only offers MultiGWAS demonstrates its utility in understanding the best genetic model behind the SNP association in tetraploid organisms. Therefore, MultiGWAS probed to be an excellent alternative for wrapping GWAS replication in diploid and tetraploid organisms in a single analysis environment.  相似文献   
135.
Vegetation History and Archaeobotany - A system of farming with an alternation of land use between being cultivated or left fallow as grassland (Feldgraswirtschaft) developed in southwestern...  相似文献   
136.
137.
Antonie van Leeuwenhoek - Strain M2T was isolated from the beach of Cuxhaven, Wadden Sea, Germany, in course of a program to attain new producers of bioactive natural products. Strain M2T produces...  相似文献   
138.
One of the common explanations for oxidative stress in the physiological milieu is based on the Fenton reaction, i.e. the assumption that radical chain reactions are initiated by metal-catalyzed electron transfer to hydrogen peroxide yielding hydroxyl radicals. On the other hand — especially in the context of so-called “iron switches” — it is postulated that cellular signaling pathways originate from the interaction of reduced iron with hydrogen peroxide.

Using fluorescence detection and EPR for identification of radical intermediates, we determined the rate of iron complexation by physiological buffer together with the reaction rate of concomitant hydroxylations of aromatic compounds under aerobic and anaerobic conditions. With the obtained overall reaction rate of 1,700 M-1s-1 for the buffer-dependent reactions and the known rates for Fenton reactions, we derive estimates for the relative reaction probabilities of both processes.

As a consequence we suggest that under in vivo conditions initiation of chain reactions by hydroxyl radicals generated by the Fenton reaction is of minor importance and hence metal-dependent oxidative stress must be rather independent of the so-called “peroxide tone”. Furthermore, it is proposed that — in the low (subtoxic) concentration range — hydroxylated compounds derived from reactions of “non-free” (crypto) OH radicals are better candidates for iron-dependent sensing of redox-states and for explaining the origin of cellular signals than the generation of “free” hydroxyl radicals.  相似文献   
139.
Helicobacter felis belongs to the fastidious gastric non‐Helicobacter pylori helicobacter species that are typically found in the stomach of cats and dogs. These bacteria have the potential to colonize the human stomach and are then associated with gastritis, gastroduodenal ulcers, and MALT lymphoma. Strains cultured from the human stomach are rare. Here, we present the first isolation of H. felis from a gastric biopsy specimen of a 14‐year‐old girl who presented with persistent epigastric pain. The strain was cultured using our routine protocol for H. pylori and identified by phylogenetic analyses of partial urease AB and gyrB gene sequences.  相似文献   
140.
Cancer is a leading cause of death and alterations of glycosylation are characteristic features of malignant cells. Colorectal cancer is one of the most common cancers and its exact causes and biology are not yet well understood. Here, we compared glycosylation profiles of colorectal tumor tissues and corresponding control tissues of 13 colorectal cancer patients to contribute to the understanding of this cancer. Using MALDI-TOF(/TOF)-MS and 2-dimensional LC-MS/MS we characterized enzymatically released and 2-aminobenzoic acid labeled glycans from glycosphingolipids. Multivariate data analysis revealed significant differences between tumor and corresponding control tissues. Main discriminators were obtained, which represent the overall alteration in glycosylation of glycosphingolipids during colorectal cancer progression, and these were found to be characterized by (1) increased fucosylation, (2) decreased acetylation, (3) decreased sulfation, (4) reduced expression of globo-type glycans, as well as (5) disialyl gangliosides. The findings of our current research confirm former reports, and in addition expand the knowledge of glycosphingolipid glycosylation in colorectal cancer by revealing new glycans with discriminative power and characteristic, cancer-associated glycosylation alterations. The obtained discriminating glycans can contribute to progress the discovery of biomarkers to improve diagnostics and patient treatment.Worldwide, cancer is a leading cause of death. With estimated 1.2 million diagnoses in 2008, colorectal cancer is the third most common cancer in the world and the fourth most common cause of death with an annual mortality of ∼600 000 (1). The exact causes of colorectal cancer are unknown, but different risk factors such as age, polyps, personal and family history, ulcerative colitis, or Crohn''s colitis have been proposed (2). Standard screening procedures include flexible sigmoidoscopy, colonoscopy, and immunological fecal occult blood testing. Each of them has its advantages and drawbacks such as invasiveness or low sensitivity and specificity (3). The method of choice for the treatment of colorectal cancer is surgery and therapeutic decisions are based on the tumor, lymph node, and metastasis staging-system as a prognostic factor (4). Current research has led to improved treatment strategies of colorectal cancer, however, the clinical outcome, the progression of the disease, and the response to the treatment remain variable among individuals. The heterogeneity of colorectal cancer at the molecular level—caused by accumulation of multiple genetic changes—may be one of the main reasons for this variability (5). Genetic factors such as instabilities, but also expression levels (6) can explain part of the cancer biology, but glycomics is gaining importance to complement the overall picture as aberrant glycosylation of proteins and lipids has been shown to be correlated with disease and malignancy (7, 8).Glycosylation is involved in many biological processes and especially its functional role in cellular interaction with respect to adhesion, cell growth, and signaling is prone to be affected in cancer progression, invasion, and metastasis (9). Several cancer-associated alterations in protein glycosylation have been reported: (1) increased branching of N-glycans, (2) higher density of O-glycans, and (3) incomplete synthesis of glycans. More particularly, an increased or induced expression of GlcNAc transferase V resulting in N-glycan structures with β1–6GlcNAc antennae (5, 10), and the expression of (sialyl) Tn-antigens (11) as aberrant O-glycosylation have been reported (10).Altered glycosphingolipid (GSL)1 glycosylation of the cell surface membrane during malignancy can affect cell recognition, adhesion, and signal transduction (12) and is found to reflect: (1) incomplete synthesis with or without precursor accumulation, (2) neosynthesis (9), (3) increased sialylation, and (4) increased fucosylation (13). In many cancers, including colorectal cancer, an overexpression of the (sialyl) Lewis X antigen (10, 14) and the expression of (sialyl) Lewis A (15) are considered to be related to malignant transformation—reflecting incomplete synthesis of sialyl 6-sulfo Lewis X and disialyl Lewis A (16) as well as neosynthesis (17). Studies on gangliosides showed an overexpression of these sialylated GSLs in human malignant melanoma (18). Furthermore, the involvement of gangliosides in cell adhesion and motility was reported, which contributes to tumor metastasis (19). Specifically, the gangliosides GD3 (Hex2NeuAc2ceramide) and GM2 (Hex2HexNAc1NeuAc1ceramide) have been found to be associated with tumor-angiogenesis (19). The up-regulation of fucosyltransferases in cancer was shown to cause a higher degree of fucosylation in malignant tissues (20) and Moriwaki et al. proposed that the increase in the fucosylation for GSLs was an early event in cancer (21). Misonou et al. investigated glycans derived from GSLs in colorectal cancer tissues showing aberrant glycan structures based on linkage differences as well as increased sialylation and fucosylation compared with control tissue (22), which is in line with observed changes in GSL glycosylation with regard to cancer progression (9, 13).Recently, we investigated the N-glycosylation profiles of colorectal tumors and correlating control tissues for biomarker discovery. Statistical analyses revealed an increase of sulfated glycan structures as well as paucimannosidic glycans and glycans containing sialylated Lewis type epitopes in the tumor tissue, whereas structures with bisecting GlcNAc were found to be decreased in malignancy (23). To further progress the understanding of colorectal cancer biology and the improvement of diagnostic tools and patient treatment, we complemented this recent study on N-glycosylation by an investigation of the glycosphingolipid-derived glycans (named GSL-glycans in the following) from frozen tumor tissues and corresponding control tissues from the same 13 colorectal cancer patients. GSL-glycans were enzymatically released, labeled with 2-aminobenzoic acid (AA) and analyzed by hydrophilic interaction liquid chromatography (HILIC) with fluorescence detection as well as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Employing multivariate statistical analysis, this approach revealed an intricate GSL-glycosylation pattern of tumor tissues and specific glycosylation differences in comparison to the corresponding control tissue.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号