全文获取类型
收费全文 | 5186篇 |
免费 | 371篇 |
国内免费 | 3篇 |
专业分类
5560篇 |
出版年
2023年 | 18篇 |
2022年 | 64篇 |
2021年 | 90篇 |
2020年 | 52篇 |
2019年 | 74篇 |
2018年 | 117篇 |
2017年 | 102篇 |
2016年 | 181篇 |
2015年 | 276篇 |
2014年 | 332篇 |
2013年 | 335篇 |
2012年 | 463篇 |
2011年 | 462篇 |
2010年 | 281篇 |
2009年 | 249篇 |
2008年 | 332篇 |
2007年 | 300篇 |
2006年 | 288篇 |
2005年 | 244篇 |
2004年 | 260篇 |
2003年 | 231篇 |
2002年 | 198篇 |
2001年 | 66篇 |
2000年 | 64篇 |
1999年 | 56篇 |
1998年 | 35篇 |
1997年 | 33篇 |
1996年 | 19篇 |
1995年 | 17篇 |
1994年 | 20篇 |
1993年 | 18篇 |
1992年 | 25篇 |
1991年 | 20篇 |
1990年 | 20篇 |
1989年 | 21篇 |
1988年 | 16篇 |
1987年 | 22篇 |
1986年 | 15篇 |
1985年 | 19篇 |
1984年 | 14篇 |
1983年 | 14篇 |
1982年 | 10篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 12篇 |
1978年 | 11篇 |
1977年 | 8篇 |
1976年 | 10篇 |
1974年 | 9篇 |
1971年 | 5篇 |
排序方式: 共有5560条查询结果,搜索用时 15 毫秒
931.
932.
Adult neural precursor cells (NPCs) are predominantly located in the subventricular zone (SVZ) of the lateral ventricles or in the subgranular zone of the dentate gyrus. These NPCs produce neuroblasts that normally migrate and integrate into the olfactory bulb and hippocampus, respectively. Following CNS damage due to disease or injury, NPCs can also migrate to the site of damage. Enhancement of NPC migration to sites of neural damage may increase their potential for repair but requires an understanding of processes that regulate basal and injury-induced migration so we can harness this potential. This review highlights the extrinsic factors and major intrinsic signalling pathways that regulate endogenous basal NPC migration to the olfactory bulb and the role of inflammatory mediators and chemokines in disease and injury-induced NPC migration. 相似文献
933.
Chen YX Man K Ling GS Chen Y Sun BS Cheng Q Wong OH Lo CK Ng IO Chan LC Lau GK Lin CL Huang F Huang FP 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(9):6009-6015
The dendritic cell (DC)-based tumor immunotherapy has been a new promise of cure for cancer patients, but animal studies and clinical trials have thus far only shown limited success, especially in treating established tumors. Certain immunosuppressive mechanisms triggered by tumor cells or the derivatives are believed to be a major obstacle. We studied the role of DC-derived IL-10 and its negative impact on vaccine efficacy in mouse models. Liver tumor cells were injected via the portal vein, giving rise to disseminated intrahepatic tumors, or s.c. to form solid but extrahepatic tumors. Bone marrow-derived DCs were generated from normal or IL-10-deficient mice and used as the vector to deliver tumor Ags. We demonstrate here that DCs devoid of IL-10, a potent immunosuppressive cytokine, are superior over conventional DCs in triggering antitumor immunity. The IL-10(-/-)DCs were highly immunogenic, expressed enhanced levels of surface MHC class II molecules, and secreted increased amounts of Th1-related cytokines. By inducing tumor-specific killing and through the establishment of immunological memory, the vaccines delivered by IL-10(-/-)DCs could evoke strong therapeutic and protective immunity against hepatocellular carcinoma in the mouse models. These findings will have great clinical impact once being translated into the treatment of malignant, and potentially infectious, diseases in humans. 相似文献
934.
So-Jung Choi Sung-Hyun Kim Ho Y. Kang Jinseon Lee Jong H. Bhak Insuk Sohn Sin-Ho Jung Yong Soo Choi Hong Kwan Kim Jungho Han Nam Huh Gyusang Lee Byung C. Kim Jhingook Kim 《Biochemical and biophysical research communications》2011,(1):23
We determined the somatic mutations in the mitochondrial genomes of 70 lung cancer patients by pair-wise comparative analyses of the normal- and tumor-genome sequences acquired using Affymetrix Mitochondrial Resequencing Array 2.0. The overall mutation rates in lung cancers were Approximately 100 fold higher than those in normal cells, with significant statistical correlation with smoking (p = 0.00088). Total of 532 somatic mutations were evenly distributed in 499 positions with very low overall frequency (1.07/bp), but the non-synonymous mutations causing amino acid substitution occurred more frequently (1.83/bp), particularly at two positions, 8701 and 10398 (10.5/bp) that code for ATPase6 and NADH dehydrogenase 3, respectively. Despite the randomness or even distribution of the mutations, these two mutations occurred together in 86% of the cases. The linkage between the two most frequent mutations suggests that they were selected together, possibly due to their cooperative role during cancer development. Indeed, the mutation at 10398 was shown by Canter, Pezzotti, and their colleagues in 2009, as a risk factor for breast cancer. In this study, we identified two potential biomarkers that might be functionally linked together during the development of cancer. 相似文献
935.
Bae JS Cheong HS Kim JO Lee SO Kim EM Lee HW Kim S Kim JW Cui T Inoue I Shin HD 《Biochemical and biophysical research communications》2008,373(4):593-596
Copy number variation (CNV) is emerging as a new tool for understanding human genomic variation, but its relationship with human disease is not yet fully understood. The data for a total of 317,503 genotypes were collected for a genome-wide association study of subarachnoid aneurismal hemorrhage (SAH) in a Japanese population (cases and controls, n = 497) using Illumina HumanHap300 BeadChip®. To identify multi-allelic CNV markers, we visually inspected all genotype clusters of 317,503 SNP markers covering the whole genome using Illumina’s BeadStudio 3.0® software. As a result, we identified 597 multi-allelic CNV markers for common (copy loss frequency > 0.05) CNV regions in a Japanese population (n = 497). The identified CNV markers shared the following characteristics: enrichment of Hardy–Weinberg disequilibria, Mendelian inconsistency among families, and high missing genotype rate. All annotated information for those markers is summarized in our database (http://www.snp-genetics.com/user/srch.htm). In addition, we performed case-control association analyses of identified multi-allelic CNV markers with the risk of subarachnoid aneurysmal hemorrhage. One SNP marker (rs1242541) within a CNV region neighboring the Sel-1 suppressor of lin-12-like protein (SEL1L) was significantly associated with a risk of SAH (P = 0.0006). We also validated the CNV around rs1242541 using real-time quantitative polymerase chain reaction (PCR). Information and methods used in this study would be helpful for accurate genotyping of SNPs on CNV regions, which could be used for association analysis of SNP markers within CNV regions. 相似文献
936.
Changes in leaf cuticular waxes of sesame (Sesamum indicum L.) plants exposed to water deficit 总被引:4,自引:0,他引:4
Sesame (Sesamum indicum L.) is one of the most important oilseed crops, having seeds and oil that are highly valued as a traditional health food. The objective of this study was to evaluate leaf cuticular wax constituents across a diverse selection of sesame cultivars, and the responses of these waxes to drought-induced wilting. Water-deficit was imposed on 18 sesame cultivars by withholding irrigation for 15d during the post-flowering stage, and the effect on seed yield and leaf waxes compared with a well-watered control. Leaf cuticular waxes were dominated by alkanes (59% of total wax), with aldehydes being the next-most abundant class. Compared to well-irrigated plants, drought treatment caused an increase in wax amount on most cultivars, with only three cultivars having a notable reduction. When expressed as an average across all cultivars, drought treatment caused a 30% increase in total wax amount, with a 34% increase in total alkanes, a 13% increase in aldehydes, and a 28% increase in the total of unknowns. In all cultivars, the major alkane constituents were the C27, C29, C31, C33, and C35 homologs, whereas the major aldehydes were the C30, C32, and C34 homologs, and drought exposure had only minor effects on the chain length distribution within these and other wax classes. Drought treatments caused a large decrease in seed yield per plant, but did not affect the mean weight of individual seeds, showing that sesame responds to post-flowering drought by reducing seed numbers, but not seed size. Seed yield was inversely correlated with the total wax amount (-0.466*), indicating that drought induction of leaf wax deposition does not contribute directly to seed set. Further studies are needed to elucidate the ecological role for induction of the alkane metabolic pathway by drought in regulating sesame plant survival and seed development in water-limiting environments. 相似文献
937.
Reactive oxygen species mediate RANK signaling in osteoclasts 总被引:5,自引:0,他引:5
RANKL, a member of tumor necrosis factor (TNF) superfamily, regulates the differentiation, activation, and survival of osteoclasts through binding to its cognate receptor, RANK. RANK can interact with several TNF-receptor-associated factors (TRAFs) and activates signaling molecules including Akt, NF-kappaB, and MAPKs. Although the transient elevation of reactive oxygen species (ROS) by receptor activation has been shown to act as a cellular secondary messenger, the involvement of ROS in RANK signaling pathways has been not characterized. In this study, we found that RANKL stimulated ROS generation in osteoclasts. Pretreatment of osteoclasts with the antioxidants N-acetyl-l-cystein and glutathione reduced RANKL-induced Akt, NF-kappaB, and ERK activation. The reduced NF-kappaB activity by antioxidants was associated with decreased IKK activity and IkappaBalpha phosphorylation. In contrast, antioxidants did not prevent TNF-alpha-induced Akt and NF-kappaB activation. Pretreatment with antioxidants also significantly reduced RANKL-induced actin ring formation, required for bone resorbing activity, and osteoclast survival. Taken together, our results suggest that ROS act as mediators in RANKL-induced signaling pathways and cellular events. 相似文献
938.
T Yaguchi M Dwidar CK Byun B Leung S Lee YK Cho RJ Mitchell S Takayama 《Biomacromolecules》2012,13(9):2655-2661
We describe patterning of bacterial biofilms using polymer-based aqueous two-phase system (ATPS) microprinting protocols. The fully aqueous but selectively bacteria-partitioning nature of the ATPS allows spatially distinct localization of suspensions of bacteria such as Pseudomonas aeruginosa and Escherichia coli with high precision. The ATPS patterned bacterial suspensions form spatially distinct biofilms over time. Due to the fully aqueous and gentle noncontact printing procedures employed, coculture biofilms composed of multiple types of bacteria could be printed not only adjacent to each other but also directly over another layer of existing biofilm. In addition, the ATPS environment also allows free diffusion of small molecules between spatially distinct and localized bacterial suspensions and biofilms. This enables biofilms to chemically affect or be affected by neighboring biofilms or planktonic cells, even if they consist of different strains or species. We show that a β-lactamase producing biofilm confers ampicillin resistance to neighboring nonresistant planktonic cells, as seen by a 3,600-fold increase in survival of the ampicillin-sensitive strain. These examples demonstrate the ability of ATPS-based biofilm patterning methods to enable unique studies on commensalistic effects between bacterial species. 相似文献
939.
Hossein MS Jeong YW Kim S Kim JJ Park SW Jeong CS Hyun SH Hwang WS 《Cloning and stem cells》2008,10(3):403-408
The collection of in vivo matured canine oocytes relies on the accurate prediction of ovulation. The present study was designed to develop a protocol for the recovery of in vivo matured canine oocytes based on once daily measurements of serum progesterone (P(4)) concentrations. Blood samples (2 mL) were collected every day at 0900 h, and P(4) concentrations were analyzed using a DSL-3900 ACTIVE((R)) Progesterone Coated-Tube Radioimmunoassay Kit. The average number of oocytes at the metaphase II (M II) stage was significantly higher at or after 72 h (6.7 to 7.5) compared to 56 h (1.7) following ovulation. The highest numbers of corpora lutea, and therefore the highest numbers of oocytes, were recovered from bitches with initial ovulatory P(4) concentrations ranging from 6.0 to 8.0 ng/ mL (12.2 and 11.4, respectively) compared to from 4.0 to 4.9 ng/ mL (9.6 and 8.8, respectively; p < 0.05). The average number of M II oocytes recovered at 84 h from bitches with initial ovulatory P(4) levels of 5.0 to 5.9 ng/mL (7.7) was higher compared to bitches with P(4) levels of 4.0 to 4.9 ng/ mL (3.5) and 6.0 to 8.0 ng/ mL (4.8; p < 0.05). When oocyte recovery time was adjusted for initial ovulatory P(4) concentration, no significant difference in recovery rates or oocyte quality were observed. In conclusion, once daily measurements of P(4) can be used to predict ovulation in bitches, and oocyte recovery time should be adjusted for initial ovulatory serum P(4) concentrations. 相似文献
940.
Park PJ Chung JY Byun HG Seog DH Kim SK 《Bioscience, biotechnology, and biochemistry》2002,66(10):2279-2282
A cDNA sequence encoding a pore-forming subunit of ATP-sensitive potassium channel (Kir6.2 gene) of the bullfrog, Rana catesbeiana Shaw, termed RcKir6.2, was isolated from a liver cDNA library. The cDNA contained a single open reading frame of 1,173 bp encoding 391 amino acids with a calculated molecular mass of 42.9 kDa, which has a structural motif (a GFG motif) of the putative pore-forming loop of Kir6.2. Analysis of its phlyogenetic position revealed that the RcKir6.2 is close to Kir6.2 of rabbits. The predicted amino acid sequence shared sequence identity with Kir6.2 of Homo sapiens, Cavia porcellus, Mus musculus, Rattus norvegicus, and Oryctolagus cuniculus by 95.9, 95.6, 96.7, 96.7 and 99.7%, respectively. Expression of RcKir6.2 was detected in various tissues, including heart, kidney, liver, lung, spleen, and stomach of the bullfrog. 相似文献