全文获取类型
收费全文 | 1226篇 |
免费 | 53篇 |
出版年
2022年 | 12篇 |
2021年 | 25篇 |
2020年 | 12篇 |
2019年 | 11篇 |
2018年 | 29篇 |
2017年 | 18篇 |
2016年 | 28篇 |
2015年 | 34篇 |
2014年 | 53篇 |
2013年 | 74篇 |
2012年 | 93篇 |
2011年 | 84篇 |
2010年 | 51篇 |
2009年 | 45篇 |
2008年 | 69篇 |
2007年 | 72篇 |
2006年 | 40篇 |
2005年 | 48篇 |
2004年 | 45篇 |
2003年 | 52篇 |
2002年 | 61篇 |
2001年 | 33篇 |
2000年 | 23篇 |
1999年 | 18篇 |
1998年 | 21篇 |
1997年 | 15篇 |
1995年 | 10篇 |
1994年 | 5篇 |
1993年 | 6篇 |
1992年 | 7篇 |
1991年 | 9篇 |
1990年 | 15篇 |
1989年 | 9篇 |
1988年 | 14篇 |
1987年 | 12篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1984年 | 12篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 8篇 |
1979年 | 7篇 |
1978年 | 9篇 |
1977年 | 7篇 |
1974年 | 5篇 |
1973年 | 7篇 |
1972年 | 5篇 |
1969年 | 5篇 |
1968年 | 6篇 |
排序方式: 共有1279条查询结果,搜索用时 484 毫秒
121.
Xeroderma pigmentosum-Cockayne syndrome (XP-CS) includes facial freckling and early skin cancers typical of XP and some features typical of CS, such as mental retardation, spasticity, short stature, and hypogonadism. XP-CS does not include skeletal involvement, the facial phenotype of CS, or CNS demyelination and calcifications. We present a rare patient whose genome probably harbored a specific combination of mutations producing a rare double syndrome of XP-CS, with facial phenotype of CS, and CNS demyelination. 相似文献
122.
Semnani RT Venugopal PG Mahapatra L Skinner JA Meylan F Chien D Dorward DW Chaussabel D Siegel RM Nutman TB 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(10):7081-7089
Dysregulation of professional APC has been postulated as a major mechanism underlying Ag-specific T cell hyporesponsiveness in patients with patent filarial infection. To address the nature of this dysregulation, dendritic cells (DC) and macrophages generated from elutriated monocytes were exposed to live microfilariae (mf), the parasite stage that circulates in blood and is responsible for most immune dysregulation in filarial infections. DC exposed to mf for 24-96 h showed a marked increase in cell death and caspase-positive cells compared with unexposed DC, whereas mf exposure did not induce apoptosis in macrophages. Interestingly, 48-h exposure of DC to mf induced mRNA expression of the proapoptotic gene TRAIL and both mRNA and protein expression of TNF-alpha. mAb to TRAIL-R2, TNF-R1, or TNF-alpha partially reversed mf-induced cell death in DC, as did knocking down the receptor for TRAIL-R2 using small interfering RNA. The mf also induced gene expression of BH3-interacting domain death agonist and protein expression of cytochrome c in DC; mf-induced cleavage of BH3-interacting domain death agonist could be shown to induce release of cytochrome c, leading to activation of caspase 9. Our data suggest that mf induce DC apoptosis in a TRAIL- and TNF-alpha-dependent fashion. 相似文献
123.
Gao Y Portugal AD Liu J Negash S Zhou W Tian J Xiang R Longo LD Raj JU 《American journal of physiology. Lung cellular and molecular physiology》2008,295(5):L889-L896
The roles of Rho kinase (ROCK) and cGMP-dependent protein kinase (PKG) in cGMP-mediated relaxation of fetal pulmonary veins exposed to chronic hypoxia (CH) were investigated. Fourth generation pulmonary veins were dissected from near-term fetuses ( approximately 140 days of gestation) delivered from ewes exposed to chronic high altitude hypoxia for approximately 110 days (CH) and from control ewes. After constriction with endothelin-1, 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) caused a similar relaxation of both control and CH vessels. Rp-8-Br-PET-cGMPS (a PKG inhibitor) inhibited whereas Y-27632 (a ROCK inhibitor) augmented relaxation of control veins to 8-Br-cGMP. These effects were significantly diminished in CH veins. PKG protein expression and activity were greater whereas ROCK protein expression and activity were less in CH vessels compared with controls. Phosphorylation of threonine 696 (ROCK substrate) and serine 695 (PKG substrate) of the regulatory myosin phosphatase targeting subunit MYPT1 of myosin light chain (MLC) phosphatase was stimulated to a lesser extent in CH than in control veins by endothelin-1 (ROCK stimulant) and 8-Br-cGMP (PKG stimulant), respectively. The phosphorylation and dephosphorylation of MLC caused by endothelin-1 and 8-Br-cGMP, respectively, were less in CH veins than in controls. These results suggest that CH in utero upregulates PKG activity but attenuates PKG action in fetal pulmonary veins. These effects are offset by the diminished ROCK action on MYPT1 and MLC and thus lead to an unaltered response to cGMP. 相似文献
124.
Liu YZ Wilson SG Wang L Liu XG Guo YF Li J Yan H Deloukas P Soranzo N Chinappen-Horsley U Chinnapen-Horsley U Cervino A Cervino A Williams FM Xiong DH Zhang YP Jin TB Levy S Papasian CJ Drees BM Hamilton JJ Recker RR Spector TD Deng HW 《PloS one》2008,3(9):e3160
Osteoporosis, the most prevalent metabolic bone disease among older people, increases risk for low trauma hip fractures (HF) that are associated with high morbidity and mortality. Hip bone size (BS) has been identified as one of the key measurable risk factors for HF. Although hip BS is highly genetically determined, genetic factors underlying the trait are still poorly defined. Here, we performed the first genome-wide association study (GWAS) of hip BS interrogating approximately 380,000 SNPs on the Affymetrix platform in 1,000 homogeneous unrelated Caucasian subjects, including 501 females and 499 males. We identified a gene, PLCL1 (phospholipase c-like 1), that had four SNPs associated with hip BS at, or approaching, a genome-wide significance level in our female subjects; the most significant SNP, rs7595412, achieved a p value of 3.72x10(-7). The gene's importance to hip BS was replicated using the Illumina genotyping platform in an independent UK cohort containing 1,216 Caucasian females. Two SNPs of the PLCL1 gene, rs892515 and rs9789480, surrounded by the four SNPs identified in our GWAS, achieved p values of 8.62x10(-3) and 2.44x10(-3), respectively, for association with hip BS. Imputation analyses on our GWAS and the UK samples further confirmed the replication signals; eight SNPs of the gene achieved combined imputed p values<10(-5) in the two samples. The PLCL1 gene's relevance to HF was also observed in a Chinese sample containing 403 females, including 266 with HF and 177 control subjects. A SNP of the PLCL1 gene, rs3771362 that is only approximately 0.6 kb apart from the most significant SNP detected in our GWAS (rs7595412), achieved a p value of 7.66x10(-3) (odds ratio = 0.26) for association with HF. Additional biological support for the role of PLCL1 in BS comes from previous demonstrations that the PLCL1 protein inhibits IP3 (inositol 1,4,5-trisphosphate)-mediated calcium signaling, an important pathway regulating mechanical sensing of bone cells. Our findings suggest that PLCL1 is a novel gene associated with variation in hip BS, and provide new insights into the pathogenesis of HF. 相似文献
125.
In yeast, approximately 31 autophagy-related (Atg) proteins have been identified. Most of them reside at the phagophore assembly site (PAS), although the function of the PAS mostly remains unclear. One reason for the latter is the lack of stoichiometric information regarding the Atg proteins at this site. We report the application of fluorescence microscopy to study the amount of Atg proteins at the PAS. We find that an increase in the amount of Atg11 at the PAS enhances the recruitment of Atg8 and Atg9 to this site and facilitates the formation of more cytoplasm-to-vacuole targeting vesicles. In response to autophagy induction, the amount of most Atg proteins remains unchanged at the PAS, whereas we see an enhanced recruitment of Atg8 and 9 at this site. During autophagy, the amount of Atg8 at the PAS showed a periodic change, indicating the formation of autophagosomes. Application of this method and further analysis will provide more insight into the functions of Atg proteins. 相似文献
126.
BACKGROUND: Hydatid disease is caused by Echinococcus granulosus, endemic in cattle and sheep-raising regions of the world such as Central Europe, South America, Australia, New Zealand and South Africa. Although hydatid disease is more common in liver and lung, it also affects brain, kidney, spleen and muscle. We present a case of intraabdominal hydatid cyst, diagnosed by fine needle aspiration cytology, producing an indentation of the liver, which is uncommon. CASE: A male patient presented with right side abdominal pain. On ultrasonography an intraabdominal solid mass (right hypochondrial) was revealed, and subsequently FNA was done. Smears were diagnostic of hydatid cyst. CONCLUSION: FNAC is a sensitive and rapid technique in diagnosis of hydatid cysts. The present case is unusual, owing to its presentation as a solid abdominal mass seeding over the liver and mimicking malignancy radiologically. 相似文献
127.
128.
BACKGROUND: Tuberculosis of the thyroid is very rare and does not strike the clinician as a first clinical diagnosis of a thyroid nodule. To our knowledge, only 40 cases of tuberculous thyroiditis diagnosed by fine needle aspiration cytology (FNAC) are described in the English literature. CASE: We report a case of tuberculous thyroiditis in a young woman who presented with a right-side solitary thyroid nodule of short duration (15 days), diagnosed by FNAC and confirmed by positive immunocytochemistry with monoclonal antibody to Mycobacterium tuberculosis complex. Ziehl Neelsen staining for acid-fast bacilli (AFB) was negative. CONCLUSION: FNAC provides a confident preoperative diagnosis of thyroid tuberculosis, obviating the need for unnecessary surgical removal of thyroid nodule. Immunocytochemistry is an important diagnostic adjunct to FNAC in AFB-negative cases. 相似文献
129.
Achur RN Kakizaki I Goel S Kojima K Madhunapantula SV Goyal A Ohta M Kumar S Takagaki K Gowda DC 《Biochemistry》2008,47(47):12635-12643
Infection with Plasmodium falciparum during pregnancy results in the adherence of infected red blood cells (IRBCs) in placenta, causing pregnancy-associated malaria with severe health complications in mothers and fetuses. The chondroitin 4-sulfate (C4S) chains of very low sulfated chondroitin sulfate proteoglycans (CSPGs) in placenta mediate the IRBC adherence. While it is known that partially sulfated but not fully sulfated C4S effectively binds IRBCs, structural interactions involved remain unclear and are incompletely understood. In this study, structurally defined C4S oligosaccharides of varying sulfate contents and sizes were evaluated for their ability to inhibit the binding of IRBCs from different P. falciparum strains to CSPG purified from placenta. The results clearly show that, with all parasite strains studied, dodecasaccharide is the minimal chain length required for the efficient adherence of IRBCs to CSPG and two 4-sulfated disaccharides within this minimal structural motif are sufficient for maximal binding. Together, these data demonstrate for the first time that the C4S structural requirement for IRBC adherence is parasite strain-independent. We also show that the carboxyl group on nonreducing end glucuronic acid in dodecasaccharide motif is important for IRBC binding. Thus, in oligosaccharides containing terminal 4,5-unsaturated glucuronic acid, the nonreducing end disaccharide moiety does not interact with IRBCs due to the altered spatial orientation of carboxyl group. In such C4S oligosaccharides, 14-mer but not 12-mer constitutes the minimal motif for inhibition of IRBC binding to placental CSPG. These data have important implications for the development and evaluation of therapeutics and vaccine for placental malaria. 相似文献
130.
Salicylic acid induced physiological and biochemical changes in wheat seedlings under water stress 总被引:15,自引:0,他引:15
Salicylic acid (SA) is an important signal molecule modulating plantresponses to stress. It is recently reported to induce multiple stresstolerancein plants including drought. An experiment was, therefore, conducted toascertain the effect of salicylic acid on the growth and metabolic profile ofwheat seedlings under water stress. Irrespective of the SA concentration(1–3 mM) and water stress, SA treated plants showed, ingeneral, a higher moisture content, dry mass, carboxylase activity of Rubisco,superoxide dismutase (SOD) activity and total chlorophyll compared to those ofuntreated seedlings. SA treatment, under water stress, protected nitratereductase (NR) activity and maintained, especially at 3 mM SAconcentration, the protein and nitrogen content of leaves compared to watersufficient seedlings. Results signify the role of SA in regulating the droughtresponse of plants and suggest that SA could be used as a potential growthregulator, for improving plant growth under water stress. 相似文献