全文获取类型
收费全文 | 1327篇 |
免费 | 97篇 |
国内免费 | 1篇 |
出版年
2023年 | 7篇 |
2022年 | 22篇 |
2021年 | 63篇 |
2020年 | 25篇 |
2019年 | 38篇 |
2018年 | 32篇 |
2017年 | 28篇 |
2016年 | 37篇 |
2015年 | 75篇 |
2014年 | 86篇 |
2013年 | 90篇 |
2012年 | 127篇 |
2011年 | 97篇 |
2010年 | 69篇 |
2009年 | 63篇 |
2008年 | 68篇 |
2007年 | 69篇 |
2006年 | 54篇 |
2005年 | 59篇 |
2004年 | 63篇 |
2003年 | 39篇 |
2002年 | 51篇 |
2001年 | 10篇 |
2000年 | 10篇 |
1999年 | 8篇 |
1998年 | 9篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1994年 | 4篇 |
1992年 | 5篇 |
1991年 | 7篇 |
1990年 | 6篇 |
1989年 | 6篇 |
1987年 | 4篇 |
1982年 | 5篇 |
1980年 | 4篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1976年 | 2篇 |
1975年 | 4篇 |
1973年 | 3篇 |
1972年 | 4篇 |
1970年 | 2篇 |
1969年 | 4篇 |
1968年 | 2篇 |
1957年 | 4篇 |
1955年 | 3篇 |
1941年 | 4篇 |
1936年 | 2篇 |
1934年 | 3篇 |
排序方式: 共有1425条查询结果,搜索用时 15 毫秒
961.
Bryce D. Smith Miriam Sabin Elois Ann Berlin Larry Nackerud 《Culture, medicine and psychiatry》2009,33(3):366-381
This survey investigated the prevalence of ethnomedical syndromes and examined treatments and treatment-seeking in Mayan Guatemalans
living in United Nations High Commissioner for Refugee (UNHCR) camps in Chiapas, Mexico. Methods included a rapid ethnographic
assessment to refine survey methods and inform the cross-sectional survey, which also examined mental health outcomes; 183
households were approached for interview, representing an estimated 1,546 residents in five refugee camps and 93% of all households.
One adult per household (N = 170) was interviewed regarding his or her health; an additional 9 adults in three surveyed households participated and
were included in this analysis; of the 179 participants, 95 primary child-care providers also answered a children’s health
questionnaire for their children. Results indicated that ethnomedical syndromes were common in this sample, with 59% of adults
and 48.4% of children having experienced susto (fright condition) and 34.1% of adults reporting ataques de nervios (nervous attacks); both conditions were significantly associated with symptoms consistent with posttraumatic stress disorder,
anxiety and depression and are mental health conditions recognized by the American Psychiatric Association. Combining healthcare
provider and indigenous treatments such as physician prescribed medication (65%), medicinal plants (65.7%), and limpias (spiritual cleansings) (40.6%) was reported. Most participants (86%) sought routine medical treatment from UNHCR trained
health promoters in their camp. Assessing ethnomedical health is important for informing mental health programs among this
population. 相似文献
962.
Terashima M Takahashi M Shimoyama M Tanigawa Y Urano T Tsuchiya M 《Molecular and cellular biochemistry》2009,320(1-2):93-100
Arginine-specific ADP-ribosyltransferase (Art) catalyzes the mono-ADP-ribosylation, in which it transfers a single ADP-ribose moiety of NAD to the arginine residue(s) of target proteins, and may regulate the function of the proteins or peptides in cellular processes. In vertebrates, Art family is consisted of seven members (Arts1-7), and these Arts are distributed among various tissues except B lymphocytes. Previously, we described molecular cloning, characterization and distribution of glycosylphosphatidylinositol (GPI)-anchored Arts, Art7.1 and Art7.2 (formerly, we referred as cgArt1 and cgArt2, respectively) in chicken tissues (Terashima et al (2005) Biochem J 389:853-861). Here, we demonstrate for the first time that Art7.1 was predominantly expressed on the surface of B cells from the bursa of Fabricius as a GPI-anchored form, as well as on T cells from the thymocytes. Furthermore, we show that the expression of Art7.1 molecules on B cells could modulate the B cell receptor (BCR) signalling and direct the B cell fate to maturation. Thus, our present observation sheds light on the Art molecule expressed on B cells and its possible functional role in BCR signalling. 相似文献
963.
Mucin genes encode a family of the largest expressed proteins in the human genome. The proteins are highly substituted with O-linked oligosaccharides that greatly restrict access to the peptide backbones. The genomic organization of the N-terminal, O-glycosylated, and C-terminal regions of most of the mucins has been established and is available in the sequence databases. However, much less is known about the fate of their exposed protein regions after translation and secretion, and to date, detailed proteomic studies complementary to the genomic studies are rather limited. Using mucins isolated from cultured human airway epithelial cell secretions, trypsin digestion, and mass spectrometry, we investigated the proteome coverage of the mucins responsible for the maintenance and protection of the airway epithelia. Excluding the heavily glycosylated mucin domains, up to 85% coverage of the N-terminal region of the gel-forming mucins MUC5B and MUC5AC was achieved, and up to 60% of the C-terminal regions were covered, suggesting that more N- and sparsely O-glycosylated regions as well as possible other modifications are available at the C-terminus. All possible peptides from the cysteine-rich regions that interrupt the heavily glycosylated mucin domains were identified. Interestingly, 43 cleavage sites from 10 different domains of MUC5B and MUC5AC were identified, which possessed a non-tryptic cleavage site on the N-terminal end of the peptide, indicating potential exposure to proteolytic and/or "spontaneous cleavages". Some of these non-tryptic cleavages may be important for proper maturation of the molecule, before and/or after secretion. Most of the peptides identified from MUC16 were from the SEA region. Surprisingly, three peptides were clearly identified from its heavily glycosylated regions. Up to 25% coverage of MUC4 was achieved covering seven different domains of the molecule. All peptides from the MUC1 cytoplasmic domain were detected along with the three non-tryptic cleavages in the region. Only one peptide was identified from MUC20, which led us to successful antisera raised against the molecule. Taken together, this report represents our current efforts to dissect the complexities of mucin macromolecules. Identification of regions accessible to proteolysis can help in the design of effective antibodies and points to regions that might be available for mucin-protein interactions and identification of cleavage sites will enable understanding of their pre- and post-secretory processing in normal and disease environments. 相似文献
964.
Greathouse KL Bredfeldt T Everitt JI Lin K Berry T Kannan K Mittelstadt ML Ho SM Walker CL 《Molecular cancer research : MCR》2012,10(4):546-557
Environmental exposures during sensitive windows of development can reprogram normal physiologic responses and alter disease susceptibility later in life in a process known as developmental reprogramming. For example, exposure to the xenoestrogen diethylstilbestrol during reproductive tract development can reprogram estrogen-responsive gene expression in the myometrium, resulting in hyperresponsiveness to hormone in the adult uterus and promotion of hormone-dependent uterine leiomyoma. We show here that the environmental estrogens genistein, a soy phytoestrogen, and the plasticizer bisphenol A, differ in their pattern of developmental reprogramming and promotion of tumorigenesis (leiomyomas) in the uterus. Whereas both genistein and bisphenol A induce genomic estrogen receptor (ER) signaling in the developing uterus, only genistein induced phosphoinositide 3-kinase (PI3K)/AKT nongenomic ER signaling to the histone methyltransferase enhancer of zeste homolog 2 (EZH2). As a result, this pregenomic signaling phosphorylates and represses EZH2 and reduces levels of H3K27me3 repressive mark in chromatin. Furthermore, only genistein caused estrogen-responsive genes in the adult myometrium to become hyperresponsive to hormone; estrogen-responsive genes were repressed in bisphenol A-exposed uteri. Importantly, this pattern of EZH2 engagement to decrease versus increase H3K27 methylation correlated with the effect of these xenoestrogens on tumorigenesis. Developmental reprogramming by genistein promoted development of uterine leiomyomas, increasing tumor incidence and multiplicity, whereas bisphenol A did not. These data show that environmental estrogens have distinct nongenomic effects in the developing uterus that determines their ability to engage the epigenetic regulator EZH2, decrease levels of the repressive epigenetic histone H3K27 methyl mark in chromatin during developmental reprogramming, and promote uterine tumorigenesis. 相似文献
965.
966.
967.
Carroll RK Robison TM Rivera FE Davenport JE Jonsson IM Florczyk D Tarkowski A Potempa J Koziel J Shaw LN 《Microbes and infection / Institut Pasteur》2012,14(11):989-999
Staphylococcus aureus is a highly virulent bacterial pathogen capable of causing a variety of ailments throughout the human body. It is a major public health concern due to the continued emergence of highly pathogenic methicillin resistant strains (MRSA) both within hospitals and in the community. Virulence in S. aureus is mediated by an array of secreted and cell wall associated virulence factors, including toxins, hemolysins and proteases. In this work we identify a leucine aminopeptidase (LAP, pepZ) that strongly impacts the pathogenic abilities of S. aureus. Disruption of the pepZ gene in either Newman or USA300 resulted in a dramatic attenuation of virulence in both localized and systemic models of infection. LAP is required for survival inside human macrophages and gene expression analysis shows that pepZ expression is highest in the intracellular environment. We examine the cellular location of LAP and demonstrate that it is localized to the bacterial cytosol. These results identify for the first time an intracellular leucine aminopeptidase that influences disease causation in a Gram-positive bacterium. 相似文献
968.
DS Eom S Inoue LB Patterson TN Gordon R Slingwine S Kondo M Watanabe DM Parichy 《PLoS genetics》2012,8(8):e1002899
The zebrafish adult pigment pattern has emerged as a useful model for understanding the development and evolution of adult form as well as pattern-forming mechanisms more generally. In this species, a series of horizontal melanophore stripes arises during the larval-to-adult transformation, but the genetic and cellular bases for stripe formation remain largely unknown. Here, we show that the seurat mutant phenotype, consisting of an irregular spotted pattern, arises from lesions in the gene encoding Immunoglobulin superfamily member 11 (Igsf11). We find that Igsf11 is expressed by melanophores and their precursors, and we demonstrate by cell transplantation and genetic rescue that igsf11 functions autonomously to this lineage in promoting adult stripe development. Further analyses of cell behaviors in vitro, in vivo, and in explant cultures ex vivo demonstrate that Igsf11 mediates adhesive interactions and that mutants for igsf11 exhibit defects in both the migration and survival of melanophores and their precursors. These findings identify the first in vivo requirements for igsf11 as well as the first instance of an immunoglobulin superfamily member functioning in pigment cell development and patterning. Our results provide new insights into adult pigment pattern morphogenesis and how cellular interactions mediate pattern formation. 相似文献
969.
970.