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   1695篇
  免费   150篇
  国内免费   29篇
  1874篇
  2023年   23篇
  2022年   64篇
  2021年   72篇
  2020年   40篇
  2019年   49篇
  2018年   62篇
  2017年   51篇
  2016年   63篇
  2015年   79篇
  2014年   100篇
  2013年   109篇
  2012年   148篇
  2011年   141篇
  2010年   77篇
  2009年   61篇
  2008年   105篇
  2007年   76篇
  2006年   74篇
  2005年   59篇
  2004年   39篇
  2003年   36篇
  2002年   34篇
  2001年   22篇
  2000年   23篇
  1999年   26篇
  1998年   19篇
  1997年   10篇
  1996年   7篇
  1994年   5篇
  1993年   9篇
  1992年   20篇
  1991年   12篇
  1990年   13篇
  1989年   9篇
  1988年   10篇
  1987年   10篇
  1986年   5篇
  1985年   8篇
  1984年   5篇
  1983年   8篇
  1982年   7篇
  1981年   8篇
  1979年   7篇
  1978年   6篇
  1977年   5篇
  1976年   7篇
  1974年   4篇
  1973年   12篇
  1971年   10篇
  1966年   5篇
排序方式: 共有1874条查询结果,搜索用时 9 毫秒
101.
Technologies allowing direct detection of specific RNA/DNA sequences occasionally serve as an alternative to amplification methods for gene expression studies. In these direct methods the hybridization of probes takes place in complex mixtures, thus specificity and sensitivity still limit the use of current technologies. To address these challenges, we developed a new technique called the nucleic acid capture assay, involving a direct multi-capture system. This approach combines a 3′-ethylene glycol scaffolding with the incorporation of 2′-methoxy deoxyribonucleotides in the capture sequences. In our design, all nucleotides other than those complementary to the target mRNA have been replaced by an inert linker, resulting in significant reductions in non-specific binding. We also provide a versatile method to detect the presence of captured targets by using specific labeled probes with alkaline phosphatase-conjugated anti-label antibodies. This direct, flexible and reliable technique for gene expression analysis is well suited for high-throughput screening and has potential for DNA microarray applications.  相似文献   
102.
Studies of mucins suggest that the structural effects of O-glycans are restricted to steric interactions between peptide-linked GalNAc residues and adjacent polypeptide residues. It has been proposed, however, that differential O-glycan sialylation alters the structure of the stalk-like region of the T cell co-receptor, CD8, and that this, in turn, modulates ligand binding (Daniels, M. A., Devine, L., Miller, J. D., Moser, J. M., Lukacher, A. E., Altman, J. D., Kavathas, P., Hogquist, K. A., and Jameson, S. C. (2001) Immunity 15, 1051-1061; Moody, A. M., Chui, D., Reche, P. A., Priatel, J. J., Marth, J. D., and Reinherz, E. L. (2001) Cell 107, 501-512). We characterize the glycosylation of soluble, chimeric forms of the alphaalpha- and alphabeta-isoforms of murine CD8 containing the O-glycosylated stalk of rat CD8alphaalpha, and we show that the stalk O-glycans are differentially sialylated in CHO K1 versus Lec3.2.8.1 cells (82 versus approximately 6%, respectively). Sedimentation analysis indicates that the Perrin functions, Pexp, which reflect overall molecular shape, are very similar (1.61 versus 1.54), whereas the sedimentation coefficients (s) of the CHO K1- and Lec3.2.8.1-derived proteins differ considerably (3.73 versus 3.13 S). The hydrodynamic properties of molecular models also strongly imply that the sialylated and non-sialylated forms of the chimera have parallel, equally highly extended stalks ( approximately 2.6 A/residue). Our analysis indicates that, as in the case of mucins, the overall structure of O-glycosylated stalk-like peptides is sialylation-independent and that the functional effects of differential CD8 O-glycan sialylation need careful interpretation.  相似文献   
103.
The complex and dynamic pattern of Hoxb3 expression in the developing hindbrain and the associated neural crest of mouse embryos is controlled by three separate cis-regulatory elements: element I (region A), element IIIa, and the r5 enhancer (element IVa). We have examined the cis-regulatory element IIIa by transgenic and mutational analysis to determine the upstream trans-acting factors and mechanisms that are involved in controlling the expression of the mouse Hoxb3 gene in the anterior spinal cord and hindbrain up to the r5/r6 boundary, as well as the associated neural crest which migrate to the third and posterior branchial arches and to the gut. By deletion analysis, we have identified the sequence requirements within a 482-bp element III482. Two Hox binding sites are identified in element III482 and we have shown that in vitro both Hoxb3 and Hoxb4 proteins can interact with these Hox binding sites, suggesting that auto/cross-regulation is required for establishing the expression of Hoxb3 in the neural tube domain. Interestingly, we have identified a novel GCCAGGC sequence motif within element III482, which is also required to direct gene expression to a subset of the expression domains except for rhombomere 6 and the associated neural crest migrating to the third and posterior branchial arches. Element III482 can direct a higher level of reporter gene expression in r6, which led us to investigate whether kreisler is involved in regulating Hoxb3 expression in r6 through this element. However, our transgenic and mutational analysis has demonstrated that, although kreisler binding sites are present, they are not required for the establishment or maintenance of reporter gene expression in r6. Our results have provided evidence that the expression of Hoxb3 in the neural tube up to the r5/r6 boundary is auto/cross-regulated by Hox genes and expression of Hoxb3 in r6 does not require kreisler.  相似文献   
104.
Gu M  Nguyen PT  Cao S  Lin F 《Acta cytologica》2002,46(3):560-566
BACKGROUND: The majority of glomus tumor are small, benign neoplasms that arise from modified smooth muscle cells. They usually occur in the dermis or subcutis of the extremities. However, rare cases have been reported in the visceral locations, most often in the stomach. CASE: A 32-year-old woman presented with episodes of right upper quadrant pain. She was found to have a gastric tumor that was biopsied at another hospital, where the diagnosis of gastrointestinal stromal tumor (GIST) was made. Endoscopic ultrasound (EUS) performed at our institution revealed a gastric submucosal tumor that was then biopsied by fine needle aspiration (FNA). Cytology revealed cohesive clusters of uniform, round, small cells with ill-defined cytoplasmic borders and scanty, amphophilic cytoplasm. Nuclei were round, with smooth nuclear membranes and evenly distributed, dusty chromatin. Intermingled with those epithelioid cells were small, short, spindled, normal endothelial cells. Immunohistochemical studies performed on cell block showed that the tumor cells were negative for CD34, CD117, chromogranin, synaptophysin, desmin and AE1/AE3 and were strongly positive for SMA, HHF-35 and collagen type IV. Glomus tumor was diagnosed and later confirmed by histology. CONCLUSION: EUS-guided FNA biopsy is efficient and permits adequate sampling for accurate diagnosis of gastric glomus tumor. Although rare, glomus tumor should be in the differential diagnosis among other gastric lesions, such as well-differentiated adenocarcinoma, epithelioid GIST and carcinoid tumor.  相似文献   
105.
106.
107.
We have recently found evidence for impairment of nitric oxide (NO) formation and induction of oxidative stress in residents of an endemic area of chronic arsenic poisoning in Inner Mongolia, China. To investigate the underlying mechanisms responsible for these phenomena, a subchronic animal experiment was conducted using male New Zealand White rabbits. After 18 weeks of continuous exposure of rabbits to 5 mg/l of arsenate in drinking water, a significant decrease in systemic NO production occurred, as shown by significantly reduced plasma NO metabolites levels (76% of control) and a tendency towards decreased serum cGMP levels (81.4% of control). On the other hand, increased oxidative stress, as shown by significantly increased urinary hydrogen peroxide (H(2)O(2)) (120% of control), was observed in arsenate-exposed rabbits. In additional experiments measuring aortic tension, the addition of either the calcium ionophore A23187 or acethylcholine (ACh) induced a transient vasoconstriction of aortic rings prepared from arsenate-exposed rabbits, but not in those prepared from control animals. This calcium-dependent contractility action observed in aorta rings from arsenate-exposed rabbits was markedly attenuated by the superoxide (O2(.-)) scavenging enzyme Cu, Zn-SOD, as well as diphenyleneiodonium (DPI) or N(G)-nitro-L-arginine methyl ester (L-NAME), which are inhibitors for nitric oxide synthase (NOS). However, the cyclooxygenase inhibitor indomethacin or the xanthine oxidase blocker allopurinol had no effect on this vasoconstriction. These results suggest that arsenate-mediated reduction of systemic NO may be associated with the enzymatic uncoupling reaction of NOS with a subsequent enhancement of reactive oxygen species such as O2(.-), an endothelium-derived vasoconstricting factor. Furthermore, hepatic levels of (6R)-5,6,7,8-tetrahydro-L-biopterin (BH(4)), a cofactor for NOS, were markedly reduced in arsenate-exposed rabbits to 62% of control, while no significant change occurred in cardiac L-arginine levels. These results suggest that prolonged exposure of rabbits to oral arsenate may impair the bioavailability of BH(4) in endothelial cells and, as a consequence, disrupt the balance between NO and O2(.-) produced from endothelial NOS, such that enhanced free radicals are produced at the expense of NO.  相似文献   
108.
The parallel synthesis and antibacterial activity of 5-hydroxy[1,2,5] oxadiazolo[3,4-b]pyrazines is reported. The compounds were synthesized by condensing diaminofurazan with alpha-keto acids to give a variety of aryl-substituted analogues. Halogenated phenyl groups at C-6 give rise to the greatest Haemophilus influenzae antibacterial activity.  相似文献   
109.
Exposure to 2,4,6-trinitrotoluene (TNT) has been shown to cause induction of cataract in which oxidative stress plays a critical role. From bovine lens we purified to homogeneity and identified an enzyme that catalyzes the reduction of TNT, resulting in the production of reactive oxygen species. The final preparation of TNT reductase showed a single band with a subunit molecular weight of 38 kDa on SDS-PAGE. Sequence data from peptides obtained by digestion with lysylendopeptidase Achromobacter protease I (API) revealed that TNT reductase is identical to zeta-crystallin. Superoxide anions were formed during reduction of TNT by zeta-crystallin, though negligible enzyme activity or protein content for superoxide dismutase, a superoxide scavenging enzyme, was found in the lens. Thus, the present results suggest that the induction of cataracts by TNT may be associated with increased oxidative stress, as a result of reductive activation of TNT generating superoxide anions, there being minimal antioxidant enzyme activity for defense against reactive oxygen species exogenously produced in the lens.  相似文献   
110.
The mosquito sampling efficiency of CDC (Centers for Disease Control) miniature light traps hung adjacent to mosquito nets, was compared with that of both indoor and outdoor human-bait collections in ten villages in the Wosera area of Papua New Guinea. The most frequently collected anopheline in the matched indoor and light trap samples was Anopheles koliensis Owen, followed by A. punctulatus D?nitz, A. karwari (James), A. farauti Laveran (sensu lato), A. longirostris Brug and A. bancroftii Giles. All species were much less frequent in the light traps than in landing catches. The hypothesis that the numbers of mosquitoes in light traps are proportional to human landing catches was examined using regression models that allowed for sampling error in both entomological measurements. Light traps under-sampled A. punctulatus and A. farauti s.l. at high densities. The models indicated that the ratio of light trap to landing catch females of A. koliensis and A. karwari increased with increasing mosquito density. Light trap catches of A. longirostris were proportional to indoor landing rates but when outdoor landing rates were high this species was under-sampled by light traps. Numbers of A. bancroftii in light traps were found to be proportional to those in outdoor landing catches, but were negatively related to those attempting to bite indoors. Circumsporozoite positivity rates for both Plasmodium falciparum Welch and P. vivax (Grassi & Feletti) in A. punctulatus and A. farauti s.l. were significantly higher in light trap collections than in either indoor or outdoor landing catches, suggesting that light traps may selectively sample older mosquitoes of these species.  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