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   18362篇
  免费   1910篇
  国内免费   6篇
  20278篇
  2022年   211篇
  2021年   391篇
  2020年   211篇
  2019年   277篇
  2018年   336篇
  2017年   288篇
  2016年   487篇
  2015年   862篇
  2014年   894篇
  2013年   1022篇
  2012年   1344篇
  2011年   1312篇
  2010年   804篇
  2009年   704篇
  2008年   1000篇
  2007年   1002篇
  2006年   959篇
  2005年   868篇
  2004年   832篇
  2003年   785篇
  2002年   705篇
  2001年   249篇
  2000年   187篇
  1999年   221篇
  1998年   259篇
  1997年   160篇
  1996年   174篇
  1995年   168篇
  1994年   154篇
  1993年   159篇
  1992年   185篇
  1991年   140篇
  1990年   159篇
  1989年   134篇
  1988年   140篇
  1987年   125篇
  1986年   104篇
  1985年   104篇
  1984年   127篇
  1983年   127篇
  1982年   111篇
  1981年   104篇
  1980年   105篇
  1979年   94篇
  1978年   73篇
  1977年   72篇
  1976年   80篇
  1975年   75篇
  1974年   95篇
  1973年   72篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
161.
Objective: Prior studies have reported ethnic differences in adiponectin and ghrelin, but few have assessed the role of body size in normoglycemic women. We compared fasting adiponectin and ghrelin concentrations in normoglycemic 40‐ to 80‐year‐old Filipino, African‐American, and white women. Methods: Participants included women from the Rancho Bernardo Study (n = 143), the University of California‐San Diego Filipino Women's Health Study (n = 136), and the Health Assessment Study of African‐American Women (n = 212). A 2‐hour oral glucose tolerance test was administered; glucose, insulin, lipid, and anthropometric measurements were obtained. Fasting adiponectin and ghrelin were measured by radioimmunoassay. Results: Whites and Filipinas had similar BMI (23.7 and 24.3 kg/m2, respectively), waist girth (75.6 and 77.2 cm, respectively), and total body fat (27.4 and 28.5%, respectively); African‐Americans had significantly larger BMI (28.8 kg/m2), waist girth (86.3 cm), and body fat (39.6%, p < 0.0001). Adiponectin was lower in Filipinas (8.90 µg/mL) and African‐Americans (9.67 µg/mL) compared with whites (15.6 µg/mL, p < 0.001) after adjusting for age, homeostasis model assessment of insulin resistance (HOMA‐IR), and waist‐to‐hip ratio. Compared with whites, Filipinas (β = ?5.06, p < 0.0001) and African‐Americans (β = ?6.85, p < 0.0001) had significantly lower adiponectin levels after adjusting for age, waist‐to‐hip ratio, HOMA‐IR, triglycerides, high‐density lipoprotein (HDL) cholesterol, exercise, and alcohol use. Ghrelin was significantly lower in Filipinas compared with African‐Americans (1146.9 vs. 1412.2 pg/mL, p < 0.001), and this observation persisted in multivariable analysis (β = ?245.4, p < 0.0001). Ghrelin levels did not differ between whites (1356.9 pg/mL) and either ethnic group. Discussion: Normoglycemic Filipino and African‐American women had significantly lower adiponectin concentrations than white women, and Filipinas had lower ghrelin levels than African‐Americans, independently of body size or indices of insulin resistance or lipids.  相似文献   
162.
The Cherokee darter Etheostoma scotti is a federally threatened fish endemic to the Etowah River system of northwest Georgia. In order to analyse the population structure and genetic diversity of this fish, eight tetranucleotide microsatellite genetic markers were developed. The marker set was applied to 13 additional darter species to test cross-species amplification and polymorphism. Successful amplification was obtained for all eight loci in each of the 13 other species of darters, with between seven and eight polymorphic loci per species.  相似文献   
163.
The liver stages of malaria are clinically silent but have a central role in the Plasmodium life cycle. Liver stages of the parasite containing thousands of merozoites grow inside hepatocytes for several days without triggering an inflammatory response. We show here that Plasmodium uses a PEXEL/VTS motif to introduce the circumsporozoite (CS) protein into the hepatocyte cytoplasm and a nuclear localization signal (NLS) to enter its nucleus. CS outcompetes NFkappaB nuclear import, thus downregulating the expression of many genes controlled by NFkappaB, including those involved in inflammation. CS also influences the expression of over one thousand host genes involved in diverse metabolic processes to create a favorable niche for the parasite growth. The presence of CS in the hepatocyte enhances parasite growth of the liver stages in vitro and in vivo. These findings have far reaching implications for drug and vaccine development against the liver stages of the malaria parasite.  相似文献   
164.
Thermotoga sp. strain RQ2 is probably a strain of Thermotoga maritima. Its complete genome sequence allows for an examination of the extent and consequences of gene flow within Thermotoga species and strains. Thermotoga sp. RQ2 differs from T. maritima in its genes involved in myo-inositol metabolism. Its genome also encodes an apparent fructose phosphotransferase system (PTS) sugar transporter. This operon is also found in Thermotoga naphthophila strain RKU-10 but no other Thermotogales. These are the first reported PTS transporters in the Thermotogales.  相似文献   
165.
Summary We have previously demonstrated that cancer patients' peripheral blood lymphocytes (PBL) allosensitized against single or pool normal donor PBL are capable of lysing fresh autologous tumor cells in a 4-h 51Cr-release assay. In this report, we present further investigations into this phenomenon. These alloactivated killer cells (A-AK cells) lysed autologous and allogeneic tumors and allogeneic but not autologous PBL. Furthermore, cold target inhibition studies demonstrated that autologous and allogeneic tumors were lysed by the same effector cells. Multiple metastases from the same patient were equivalently lysed by these A-AK cells. The presence of adherent cells and proliferation of the precursors were necessary to generate A-AK cells, although the effector cell itself was radioresistant and nonadherent. The effects of allosensitization were enhanced by the addition of lectin-free interleukin-2 preparations to the in vitro culture by partial depletion of adherent cells prior to sensitization. The A-AK effector cell was OKT3+, OKT8+, OKT4–, OKM1– and could be generated by just 3 days of allosensitization. The precursors for A-AK cells could be separated from NK cells on percoll gradients and lysis could be generated from thoracic duct lymphocytes, a population devoid of NK cells. The phenotype of the majority of the precursor cells was OKT3+, OKT4–. These allocatived PBL could be expanded in crude or lectin-free interleukin-2 without loss of cytotoxicity for fresh autologous tumor cells. Activated T cells represent a population of non-NK cells with broad lytic specificity for fresh tumor cells. Such cells may be of value in the adoptive immunotherapy of human solid tumors and may play a role in immune surveillance.  相似文献   
166.
Mechanisms of Cyclin-Dependent Kinase Inactivation by Progestins   总被引:6,自引:2,他引:6       下载免费PDF全文
The steroid hormone progesterone regulates proliferation and differentiation in the mammary gland and uterus by cell cycle phase-specific actions. In breast cancer cells the predominant effect of synthetic progestins is long-term growth inhibition and arrest in G1 phase. Progestin-mediated growth arrest of T-47D breast cancer cells was preceded by inhibition of cyclin D1-Cdk4, cyclin D3-Cdk4, and cyclin E-Cdk2 kinase activities in vitro and reduced phosphorylation of pRB and p107. This was accompanied by decreases in the expression of cyclins D1, D3, and E, decreased abundance of cyclin D1- and cyclin D3-Cdk4 complexes, increased association of the cyclin-dependent kinase (CDK) inhibitor p27 with the remaining Cdk4 complexes, and changes in the molecular masses and compositions of cyclin E complexes. In control cells cyclin E eluted from Superdex 200 as two peaks of ~120 and ~200 kDa, with the 120-kDa peak displaying greater cyclin E-associated kinase activity. Following progestin treatment, almost all of the cyclin E was in the 200-kDa, low-activity form, which was associated with the CDK inhibitors p21 and p27; this change preceded the inhibition of cell cycle progression. These data suggest preferential formation of this higher-molecular-weight, CDK inhibitor-bound form and a reduced number of cyclin E-Cdk2 complexes as mechanisms for the decreased cyclin E-associated kinase activity following progestin treatment. Ectopic expression of cyclin D1 in progestin-inhibited cells led to the reappearance of the 120-kDa active form of cyclin E-Cdk2 preceding the resumption of cell cycle progression. Thus, decreased cyclin expression and consequent increased CDK inhibitor association are likely to mediate the decreases in CDK activity accompanying progestin-mediated growth inhibition.  相似文献   
167.
High-resolution G-banding analysis has demonstrated remarkable morphological conservation of the chromosomes of the Hominidae family members (humans, chimpanzees, gorillas, and orangutans), with the most notable differences between the genomes appearing as changes in heterochromatin distribution and pericentric inversions. Pericentric inversions may have been important for the establishment of reproductive isolation and speciation of the hominoids as they diverged from a common ancestor. Here the previously published primate karyotype comparisons, coupled with the resources of the Human Genome Project, have been used to identify pericentric inversion breakpoints seen when comparing the human karyotype to that of chimpanzee. Yeast artificial chromosome (YAC) clones were used to detect, by fluorescencein situhybridization, five evolutionary pericentric inversion breakpoints present on the chimpanzee chromosome equivalents of human chromosomes 4, 9, and 12. In addition, two YACs from human 12p that detect a breakpoint in chimpanzee detect a similar rearrangement in gorilla.  相似文献   
168.
Malaria during pregnancy is associated with poor birth outcomes, particularly low birth weight. Recently, monocyte infiltration into the placental intervillous space has been identified as a key risk factor for low birth weight. However, the malaria-induced chemokines involved in recruiting and activating placental monocytes have not been identified. In this study, we determined which chemokines are elevated during placental malaria infection and the association between chemokine expression and placental monocyte infiltration. Placental malaria infection was associated with elevations in mRNA expression of three beta chemokines, macrophage-inflammatory protein 1 (MIP-1) alpha (CCL3), monocyte chemoattractant protein 1 (MCP-1; CCL2), and I-309 (CCL1), and one alpha chemokine, IL-8 (CXCL8); all correlated with monocyte density in the placental intervillous space. Placental plasma concentrations of MIP-1 alpha and IL-8 were increased in women with placental malaria and were associated with placental monocyte infiltration. By immunohistochemistry, we localized placental chemokine production in malaria-infected placentas: some but not all hemozoin-laden maternal macrophages produced MIP-1 beta and MCP-1, and fetal stromal cells produced MCP-1. In sum, local placental production of chemokines is increased in malaria, and may be an important trigger for monocyte accumulation in the placenta.  相似文献   
169.
170.
The relative importance of respiration and organic carbon release to the efficiency of carbon specific growth of Skeletonema costatum (Grev.) Clave was evaluated over a light range from 1500–15 μE · m?2· s?1. Net growth efficiency ranged from 0.45–0.69 with a maximum at 130 μE · m?2· s?1. Respiration was 93% or more of the variations in growth efficiency. Organic carbon release ranged from 0–7% of gross production and increased with light intensity. Carbon specific particulate production was a hyperbolic function of incident light intensity and was related exponentially to particulate carbon production per unit chlorophyll a. Full sunlight conditions, 1500 μE · m?2· s?1, did not induce photoinhibition of gross production. Variations in the efficiency of growth of S. costatum were minimized over a wide range of light intensities mainly because of variations in cellular pigments which permitted the efficient utilization of available light energy, and a reduction in the losses of carbon which increases the growth rate, possibly as a consequence of the recycling of respired carbon within the cell.  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