全文获取类型
收费全文 | 1406篇 |
免费 | 76篇 |
国内免费 | 39篇 |
出版年
2024年 | 3篇 |
2023年 | 26篇 |
2022年 | 40篇 |
2021年 | 45篇 |
2020年 | 39篇 |
2019年 | 23篇 |
2018年 | 37篇 |
2017年 | 31篇 |
2016年 | 37篇 |
2015年 | 31篇 |
2014年 | 40篇 |
2013年 | 81篇 |
2012年 | 33篇 |
2011年 | 31篇 |
2010年 | 34篇 |
2009年 | 52篇 |
2008年 | 68篇 |
2007年 | 63篇 |
2006年 | 47篇 |
2005年 | 45篇 |
2004年 | 63篇 |
2003年 | 42篇 |
2002年 | 52篇 |
2001年 | 36篇 |
2000年 | 47篇 |
1999年 | 45篇 |
1998年 | 46篇 |
1997年 | 30篇 |
1996年 | 32篇 |
1995年 | 26篇 |
1994年 | 22篇 |
1993年 | 29篇 |
1992年 | 26篇 |
1991年 | 28篇 |
1990年 | 15篇 |
1989年 | 15篇 |
1988年 | 30篇 |
1987年 | 11篇 |
1986年 | 16篇 |
1985年 | 19篇 |
1984年 | 15篇 |
1983年 | 6篇 |
1982年 | 9篇 |
1981年 | 9篇 |
1980年 | 16篇 |
1979年 | 8篇 |
1978年 | 4篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1973年 | 4篇 |
排序方式: 共有1521条查询结果,搜索用时 27 毫秒
101.
Unique and conserved features of genome and proteome of SARS-coronavirus,an early split-off from the coronavirus group 2 lineage 总被引:34,自引:0,他引:34
Snijder EJ Bredenbeek PJ Dobbe JC Thiel V Ziebuhr J Poon LL Guan Y Rozanov M Spaan WJ Gorbalenya AE 《Journal of molecular biology》2003,331(5):991-1004
The genome organization and expression strategy of the newly identified severe acute respiratory syndrome coronavirus (SARS-CoV) were predicted using recently published genome sequences. Fourteen putative open reading frames were identified, 12 of which were predicted to be expressed from a nested set of eight subgenomic mRNAs. The synthesis of these mRNAs in SARS-CoV-infected cells was confirmed experimentally. The 4382- and 7073 amino acid residue SARS-CoV replicase polyproteins are predicted to be cleaved into 16 subunits by two viral proteinases (bringing the total number of SARS-CoV proteins to 28). A phylogenetic analysis of the replicase gene, using a distantly related torovirus as an outgroup, demonstrated that, despite a number of unique features, SARS-CoV is most closely related to group 2 coronaviruses. Distant homologs of cellular RNA processing enzymes were identified in group 2 coronaviruses, with four of them being conserved in SARS-CoV. These newly recognized viral enzymes place the mechanism of coronavirus RNA synthesis in a completely new perspective. Furthermore, together with previously described viral enzymes, they will be important targets for the design of antiviral strategies aimed at controlling the further spread of SARS-CoV. 相似文献
102.
We present a phase diagram of the nucleosome core particle (NCP) as a function of the monovalent salt concentration and applied osmotic pressure. Above a critical pressure, NCPs stack on top of each other to form columns that further organize into multiple columnar phases. An isotropic (and in some cases a nematic) phase of columns is observed in the moderate pressure range. Under higher pressure conditions, a lamello-columnar phase and an inverse hexagonal phase form under low salt conditions, whereas a 2D hexagonal phase or a 3D orthorhombic phase is found at higher salt concentration. For intermediate salt concentrations, microphase separation occurs. The richness of the phase diagram originates from the heterogeneous distribution of charges at the surface of the NCP, which makes the particles extremely sensitive to small ionic variations of their environment, with consequences on their interactions and supramolecular organization. We discuss how the polymorphism of NCP supramolecular organization may be involved in chromatin changes in the cellular context. 相似文献
103.
Although the social organization of many of the present-day pueblos of the American Southwest is well-described in the anthropological literature, many aspects of prehistoric Puebloan social organization have received limited attention since initial investigations of postmarital residence in the 1960s and 1970s. This paper examines postmarital residence at the Chaco Canyon great house of Pueblo Bonito, using biological data. Our findings are inconsistent with the previously well-accepted hypothesis that the Pueblo II and Pueblo III occupants of the San Juan Basin conformed to a socially prescribed pattern of matrilocal residence with matrilineal descent. Univariate variance differences for nine craniometric variables indicate a pattern of increased female variability consistent with patrilocal/bilocal residence. The results of multivariate determinant ratio analyses are in agreement with the univariate results, suggesting the possibility of a patrilocal or bilocal residence preference at Pueblo Bonito. These findings are inconsistent with the notion that the female-based system of matrilocal residence with matrilineal descent observed among the present-day Western Pueblos was the ancestral Anasazi condition. 相似文献
104.
It is believed that pericentromeric heterochromatin may play a major role in the epigenetic regulation of gene expression. We have previously shown that centromeres in human peripheral blood cells aggregate into distinct "myeloid" and "lymphoid" spatial patterns, suggesting that the three-dimensional organization of centromeric heterochromatin in interphase may be ontogenically determined during hematopoietic differentiation. To investigate this possibility, the spatial patterns of association of different centromeres were analyzed in hematopoietic progenitors and compared with those in early-B and early-T cells, mature B and T lymphocytes, and, additionally, mature granulocytes and monocytes. We show that those patterns change during lymphoid differentiation, with major spatial arrangements taking place at different stages during T and B cell differentiation. Heritable patterns of centromere association are observed, which can occur either at the level of the common lymphoid progenitor, or in early-T or early-B committed cells. A correlation of the observed patterns of centromere association with the gene content of the respective chromosomes further suggests that the variation in the composition of these heterochromatic structures may contribute to the dynamic relocation of genes in different nuclear compartments during cell differentiation, which might have functional implications for cell-stage-specific gene expression. 相似文献
105.
Pioglitazone reduces monocyte adhesion to vascular endothelium under flow by modulating RhoA GTPase and focal adhesion kinase 总被引:1,自引:0,他引:1
Thiazolidinediones (TZDs), potent peroxisome proliferator-activated receptor gamma ligands, have been shown to improve endothelial function in vascular diseases. We investigated the effects of pioglitazone, a TZD, on monocyte-endothelial interaction under flow and found that pretreatment (20 mumol/l, 48 h) significantly reduced U937 adhesion to human umbilical vein endothelial cells. Integrin expression was not altered, however, the activation of RhoA GTPase was significantly reduced after treatment. Further, pioglitazone treatment significantly reduced phosphorylation of focal adhesion kinase (FAK) at 925Y, but not at 397Y, suggesting a specific role in FAK-dependent signaling. These results indicate a novel anti-inflammatory role for this compound. 相似文献
106.
The dissociation of the neuronal Golgi complex is a classical feature observed in neurodegenerative disorders including Alzheimer's disease. The goal of this study is to determine if the phosphorylation of tau protein is involved in neuronal Golgi disassembly. Primary cortical cultures were exposed to two Golgi toxins, brefeldin A (BFA) or nordihydroguaiaretic acid (NDGA). Immunocytochemical studies using the anti58 k antibody revealed that Golgi disassembly started in exposed neurons a few minutes after treatment. BFA and NDGA induced a rapid and transient increase in tau phosphorylation in a site-specific manner on immunoblots. In addition, the increase in tau phosphorylation directly correlated with a transient dissociation of tau from the cytoskeleton and a decrease of the acetylated tubulin. Furthermore, the activity of glycogen synthase kinase-3beta (GSK-3beta) increased transiently, as demonstrated by the kinase activity assay and by immunoblottings of serine-9 and tyrosine-216 phosphorylated of GSK-3beta. A decrease of the Akt phosphorylated form was also shown. The increase in tau phosphorylation was inhibited by the GSK-3beta inhibitor, lithium. Finally, morphometric studies showed that lithium partially blocked the Golgi disassembly caused by BFA or NDGA. Together these findings indicate that GSK-3beta activity and tau phosphorylation state are involved in the maintenance of the neuronal Golgi organization. 相似文献
107.
When divergence between viral species is large, the analysis and comparison of nucleotide or protein sequences are dependent
on mutation biases and multiple substitutions per site leading, among other things, to the underestimation of branch lengths
in phylogenetic trees. To avoid the problem of multiply substituted sites, a method not directly based on the nucleic or protein
sequences has been applied to retroviruses. It consisted of asking questions about genome structure or organization, and gene
function, the series of answers creating coded sequences analyzed by phylogenic software. This method recovered the principal
retroviral groups such as the lentiviruses and spumaviruses and highlighted questions and answers characteristic of each group
of retroviruses. In general, there was reasonable concordance between the coded genome methodology and that based on conventional
phylogeny of the integrase protein sequence, indicating that integrase was fixing mutations slowly enough to marginalize the
problem of multiple substitutions at sites. To a first approximation, this suggests that the acquisition of novel genetic
features generally parallels the fixation of amino acid substitutions.
Received: 18 May 2001 / Accepted: 7 September 2001 相似文献
108.
In eukaryotes, histone H1 promotes the organization of polynucleosome filaments into chromatin fibers, thus contributing to the formation of an important structural framework responsible for various DNA transaction processes. The H1 protein consists of a short N-terminal "nose," a central globular domain, and a highly basic C-terminal domain. Structure prediction of the C-terminal domain using fold recognition methods reveals the presence of an HMG-box-like fold. We recently showed by extensive site-directed and deletion mutagenesis studies that a 34 amino acid segment encompassing the three S/TPKK motifs, within the C-terminal domain, is responsible for DNA condensing properties of H1. The position of these motifs in the predicted structure corresponds exactly to the DNA-binding segments of HMG-box-containing proteins such as Lef-1 and SRY. Previous analyses have suggested that histone H1 is likely to bend DNA bound to the C-terminal domain, directing the path of linker DNA in chromatin. Prediction of the structure of this domain provides a framework for understanding the higher order of chromatin organization. 相似文献
109.
110.
The sequences of seven new Trypanosoma brucei kinetoplast DNA minicircles were obtained. A detailed comparative analysis of these sequences and those of the 18 complete kDNA minicircle sequences from T. brucei available in the database was performed. These 25 different minicircles contain 86 putative gRNA genes. The number of gRNA genes per minicircle varies from 2 to 5. In most cases, the genes are located between short imperfect inverted repeats, but in several minicircles there are inverted repeat cassettes that did not contain identifiable gRNA genes. Five minicircles contain single gRNA genes not surrounded by identifiable repeats. Two pairs of closely related minicircles may have recently evolved from common ancestors: KTMH1 and KTMH3 contained the same gRNA genes in the same order, whereas KTCSGRA and KTCSGRB contained two gRNA genes in the same order and one gRNA gene specific to each. All minicircles could be classified into two classes on the basis of a short substitution within the highly conserved region, but the minicircles in these two classes did not appear to differ in terms of gRNA content or gene organization. A number of redundant gRNAs containing identical editing information but different sequences were present. The alignments of the predicted gRNAs with the edited mRNA sequences varied from a perfect alignment without gaps to alignments with multiple mismatches. Multiple gRNAs overlapped with upstream gRNAs, but in no case was a complete set of overlapping gRNAs covering an entire editing domain obtained. We estimate that a minimum set of approximately 65 additional gRNAs would be required for complete overlapping sets. This analysis should provide a basis for detailed studies of the evolution and role in RNA editing of kDNA minicircles in this species. 相似文献