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981.
March HN Rust AG Wright NA ten Hoeve J de Ridder J Eldridge M van der Weyden L Berns A Gadiot J Uren A Kemp R Arends MJ Wessels LF Winton DJ Adams DJ 《Nature genetics》2011,43(12):1202-1209
The evolution of colorectal cancer suggests the involvement of many genes. To identify new drivers of intestinal cancer, we performed insertional mutagenesis using the Sleeping Beauty transposon system in mice carrying germline or somatic Apc mutations. By analyzing common insertion sites (CISs) isolated from 446 tumors, we identified many hundreds of candidate cancer drivers. Comparison to human data sets suggested that 234 CIS-targeted genes are also dysregulated in human colorectal cancers. In addition, we found 183 CIS-containing genes that are candidate Wnt targets and showed that 20 CISs-containing genes are newly discovered modifiers of canonical Wnt signaling. We also identified mutations associated with a subset of tumors containing an expanded number of Paneth cells, a hallmark of deregulated Wnt signaling, and genes associated with more severe dysplasia included those encoding members of the FGF signaling cascade. Some 70 genes had co-occurrence of CIS pairs, clustering into 38 sub-networks that may regulate tumor development. 相似文献
982.
Emerging topics and new perspectives on HLA-G 总被引:1,自引:1,他引:0
Fainardi E Castellazzi M Stignani M Morandi F Sana G Gonzalez R Pistoia V Baricordi OR Sokal E Peña J 《Cellular and molecular life sciences : CMLS》2011,68(3):433-451
Following the Fifth International Conference on non-classical HLA-G antigens (HLA-G), held in Paris in July 2009, we selected
some topics which focus on emerging aspects in the setting of HLA-G functions. In particular, HLA-G molecules could play a
role in: (1) various inflammatory disorders, such as multiple sclerosis, intracerebral hemorrhage, gastrointestinal, skin
and rheumatic diseases, and asthma, where they may act as immunoregulatory factors; (2) the mechanisms to escape immune surveillance
utilized by several viruses, such as human cytomegalovirus, herpes simplex virus type 1, rabies virus, hepatitis C virus,
influenza virus type A and human immunodeficiency virus 1 (HIV-1); and (3) cytokine/chemokine network and stem cell transplantation,
since they seem to modulate cell migration by the downregulation of chemokine receptor expression and mesenchymal stem cell
activity blocking of effector cell functions and the generation of regulatory T cells. However, the immunomodulatory circuits
mediated by HLA-G proteins still remain to be clarified. 相似文献
983.
Studies were undertaken to examine the degree of divergence in four populations of pika in Colorado. Separation of blood proteins was accomplished utilizing acrylamide - gel disc electrophoresis. Separate analyses of variance were carried out for the relative mobilities of two of the transferrins (designated RM β 1 and RM β 2 ), the mean relative distance difference of the two transferrins (DM), and the density of the most prominent albumin ( α 1 ) and transferrin ( β 2 ) bands. Although the four populations were characterized by a general similarity of the gel patterns, both interpopulational and sexual variations were observed. Variations between the sexes had to do with the amounts of protein, not with differences in protein mobility. The only significant populational differences were found in reference to density and DM. The interpopulational differences may serve as an indicator of populational divergence that has not been indicated by standard morphological characters. The significant patterns of variation observed in the blood proteins of the four populations studied may reflect a lack of gene now between isolated populations. 相似文献
984.
Gross energy, digestible energy, crude protein, and digestible crude protein were estimated for two leporids and five rodents that were the primary prey of coyotes ( Canis latrans ) in southeastern Idaho. Digestible protein estimates differed (38%–54%) more than digestible energy (3.5–4.4 kcal), in the prey examined. 相似文献
985.
The ABBA family of aromatic prenyltransferases: broadening natural product diversity 总被引:1,自引:0,他引:1
Tello M Kuzuyama T Heide L Noel JP Richard SB 《Cellular and molecular life sciences : CMLS》2008,65(10):1459-1463
986.
Boyden LM Lewis JM Barbee SD Bas A Girardi M Hayday AC Tigelaar RE Lifton RP 《Nature genetics》2008,40(5):656-662
B cells, alphabeta T cells and gammadelta T cells are conserved lymphocyte subtypes encoding their antigen receptors from somatically rearranged genes. alphabeta T cells undergo positive selection in the thymus by engagement of their T cell receptors (TCRs) with self-peptides presented by major histocompatibility complex molecules. The molecules that select gammadelta T cells are unknown. Vgamma5+Vdelta1+ cells comprise 90% of mouse epidermal gammadelta T cells. By mapping and genetic complementation using a strain showing loss of Vgamma5+Vdelta1+ cells due to a failure of thymic selection, we show that this defect is caused by mutation in Skint1, a newly identified gene expressed in thymus and skin that encodes a protein with immunoglobulin-like and transmembrane domains. Skint1 is the prototypic member of a rapidly evolving family of at least 11 genes in mouse, with greatest similarity to the butyrophilin genes. These findings define a new family of proteins mediating key epithelial-immune interactions. 相似文献
987.
Unger S Böhm D Kaiser FJ Kaulfuss S Borozdin W Buiting K Burfeind P Böhm J Barrionuevo F Craig A Borowski K Keppler-Noreuil K Schmitt-Mechelke T Steiner B Bartholdi D Lemke J Mortier G Sandford R Zabel B Superti-Furga A Kohlhase J 《Nature genetics》2008,40(3):287-289
We identified four girls with a consistent constellation of facial dysmorphism and malformations previously reported in a single mother-daughter pair. Toe syndactyly, telecanthus and anogenital and renal malformations were present in all affected individuals; thus, we propose the name 'STAR syndrome' for this disorder. Using array CGH, qPCR and sequence analysis, we found causative mutations in FAM58A on Xq28 in all affected individuals, suggesting an X-linked dominant inheritance pattern for this recognizable syndrome. 相似文献
988.
Jérémy Nigri Christian Bressy Julie Roques Coraline Kozaczyk Jérôme Cros Daniel Pietrasz Raphaël Maréchal Jean-Luc Van Laethem Juan Iovanna Richard Tomasini 《Cellular and molecular life sciences : CMLS》2017,74(22):4231-4243
Pancreatic ductal adenocarcinoma (PDA) is a fatal and insidious malignant disease for which clinicians’ tools are restricted by the current limits in knowledge of how tumor and stromal cells act during the disease. Among PDA hallmarks, neural remodeling (NR) and perineural invasion (PNI) drastically influence quality of life and patient survival. Indeed, NR and PNI are associated with neuropathic pain and metastasis, respectively, both of which impact clinicians’ decisions and therapeutic options. The aim of this study was to determine the impact and clinical relevance of the peritumoral microenvironment, through pancreatitis-associated protein (PAP/REG3A) expression, on PNI in pancreatic cancer. First, we demonstrated that, in PDA, PAP/REG3A is produced by inflamed acinar cells from the peritumoral microenvironment and then enhances the migratory and invasive abilities of cancer cells. More specifically, using perineural ex vivo assays we revealed that PAP/REG3A favors PNI through activation of the JAK/STAT signaling pathway in cancer cells. Finally, we analyzed the level of PAP/REG3A in blood from healthy donors or patients with PDA from three independent cohorts. Patients with high levels of PAP/REG3A had overall shorter survival as well as poor surgical outcomes with reduced disease-free survival. Our study provides a rationale for using the PAP/REG3A level as a biomarker to improve pancreatic cancer prognosis. It also suggests that therapeutic targeting of PAP/REG3A activity in PDA could limit tumor cell aggressiveness and PNI. 相似文献
989.
Lili Li Jianming Ying Xin Tong Lan Zhong Xianwei Su Tingxiu Xiang Xingsheng Shu Rong Rong Lei Xiong Hongyu Li Anthony T. C. Chan Richard F. Ambinder Yajun Guo Qian Tao 《Cellular and molecular life sciences : CMLS》2014,71(11):2179-2192
Through subtraction of tumor-specific CpG methylation, we identified receptor tyrosine kinase-like orphan receptor 2 (ROR2) as a candidate tumor suppressor gene (TSG). ROR2 is a specific receptor or co-receptor for WNT5A, involved in canonical and non-canonical WNT signaling, with its role in tumorigenesis controversial. We characterized its functions and related cell signaling in common carcinomas. ROR2 was frequently silenced by promoter CpG methylation in multiple carcinomas including nasopharyngeal, esophageal, gastric, colorectal, hepatocellular, lung, and breast cancers, while no direct correlation of ROR2 and WNT5A expression was observed. Ectopic expression of ROR2 resulted in tumor suppression independent of WNT5A status, through inhibiting tumor cell growth and inducing cell cycle arrest and apoptosis. ROR2 further suppressed epithelial-mesenchymal transition and tumor cell stemness through repressing β-catenin and AKT signaling, leading to further inhibition of tumor cell migration/invasion and increased chemo-sensitivity. Thus ROR2, as an epigenetically inactivated TSG, antagonizes both β-catenin and AKT signaling in multiple tumorigenesis. Its epigenetic silencing could be a potential tumor biomarker and therapeutic target for carcinomas. 相似文献
990.
John Wright Richard A. Kahn Elizabeth Sztul 《Cellular and molecular life sciences : CMLS》2014,71(18):3419-3438
Eukaryotic cells require selective sorting and transport of cargo between intracellular compartments. This is accomplished at least in part by vesicles that bud from a donor compartment, sequestering a subset of resident protein “cargos” destined for transport to an acceptor compartment. A key step in vesicle formation and targeting is the recruitment of specific proteins that form a coat on the outside of the vesicle in a process requiring the activation of regulatory GTPases of the ARF family. Like all such GTPases, ARFs cycle between inactive, GDP-bound, and membrane-associated active, GTP-bound, conformations. And like most regulatory GTPases the activating step is slow and thought to be rate limiting in cells, requiring the use of ARF guanine nucleotide exchange factor (GEFs). ARF GEFs are characterized by the presence of a conserved, catalytic Sec7 domain, though they also contain motifs or additional domains that confer specificity to localization and regulation of activity. These domains have been used to define and classify five different sub-families of ARF GEFs. One of these, the BIG/GBF1 family, includes three proteins that are each key regulators of the secretory pathway. GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs and thus these GEFs are the upstream regulators that define the site and timing of vesicle production. Paradoxically, while we have detailed molecular knowledge of how GEFs activate ARFs, we know very little about how GEFs are recruited and/or activated at the right time and place to initiate transport. This review summarizes the current knowledge of GEF regulation and explores the still uncertain mechanisms that position GEFs at “budding ready” membrane sites to generate highly localized activated ARFs. 相似文献