全文获取类型
收费全文 | 74511篇 |
免费 | 6314篇 |
国内免费 | 1435篇 |
专业分类
82260篇 |
出版年
2023年 | 414篇 |
2022年 | 1103篇 |
2021年 | 1768篇 |
2020年 | 1140篇 |
2019年 | 1444篇 |
2018年 | 1849篇 |
2017年 | 1417篇 |
2016年 | 2346篇 |
2015年 | 3738篇 |
2014年 | 4228篇 |
2013年 | 4773篇 |
2012年 | 6023篇 |
2011年 | 5760篇 |
2010年 | 3558篇 |
2009年 | 3234篇 |
2008年 | 4346篇 |
2007年 | 4039篇 |
2006年 | 3680篇 |
2005年 | 3282篇 |
2004年 | 3204篇 |
2003年 | 2773篇 |
2002年 | 2361篇 |
2001年 | 1989篇 |
2000年 | 1806篇 |
1999年 | 1458篇 |
1998年 | 712篇 |
1997年 | 614篇 |
1996年 | 545篇 |
1995年 | 507篇 |
1994年 | 413篇 |
1993年 | 361篇 |
1992年 | 728篇 |
1991年 | 584篇 |
1990年 | 554篇 |
1989年 | 541篇 |
1988年 | 450篇 |
1987年 | 436篇 |
1986年 | 345篇 |
1985年 | 356篇 |
1984年 | 303篇 |
1983年 | 237篇 |
1982年 | 199篇 |
1981年 | 169篇 |
1980年 | 163篇 |
1979年 | 222篇 |
1978年 | 199篇 |
1977年 | 179篇 |
1976年 | 171篇 |
1974年 | 196篇 |
1972年 | 155篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
921.
922.
Feng En Lo Po Jung Lu Min Kuang Tsai June Han Lee Christopher Wen Chi Pang Wen Jackson Pui Man Wai Chwen Keng Tsao Po Huang Chiang Shu Yu Lyu Ko Lu Ma Ying-Chen Chi Chu-Shiu Li Chwen-Chi Liu Xifeng Wu 《PloS one》2016,11(4)
ObjectiveTo assess the benefits of regular exercise in reducing harms associated with betel quid (BQ) chewing.MethodsThe study cohort, 419,378 individuals, participated in a medical screening program between 1994 and 2008, with 38,324 male and 1,495 female chewers, who consumed 5–15 quids of BQ a day. Physical activity of each individual, based on “MET-hour/week”, was classified as “inactive” or “active”, where activity started from a daily 15 minutes/day or more of brisk walking (≥3.75 MET-hour/week). Hazard ratios for mortality and remaining years in life expectancy were calculated.ResultsNearly one fifth (18.7%) of men, but only 0.7% of women were chewers. Chewers had a 10-fold increase in oral cancer risk; and a 2-3-fold increase in mortality from lung, esophagus and liver cancer, cardiovascular disease, and diabetes, with doubling of all-cause mortality. More than half of chewers were physically inactive (59%). Physical activity was beneficial for chewers, with a reduction of all-cause mortality by 19%. Inactive chewers had their lifespan shortened by 6.3 years, compared to non-chewers, but being active, chewers improved their health by gaining 2.5 years. The improvement, however, fell short of offsetting the harms from chewing.ConclusionsChewers had serious health consequences, but being physically active, chewers could mitigate some of these adverse effects, and extend life expectancy by 2.5 years and reduce mortality by one fifth. Encouraging exercise, in addition to quitting chewing, remains the best advice for 1.5 million chewers in Taiwan. 相似文献
923.
The molecular weight and concentration of dextran sulfate affect cell growth and antibody production in CHO cell cultures 下载免费PDF全文
Jin Hyoung Park Myung Sin Lim Ju Rang Woo Jong Won Kim Gyun Min Lee 《Biotechnology progress》2016,32(5):1113-1122
To investigate the effect of dextran sulfate (DS), a widely used anti‐aggregation agent, on cell growth and monoclonal antibody (mAb) production including the quality attributes, DS with the three different MWs (4,000 Da, 15,000 Da, and 40,000 Da) at various concentrations (up to 1 g/L) was added to suspension cultures of two different recombinant CHO (rCHO) cell lines producing mAb, SM‐0.025 and CS13‐1.00. For both cell lines, the addition of DS, regardless of the MW and concentration of DS used, improved cell growth and viability in the decline phase of growth. However, it increased mAb production only in the CS13‐1.00 cells. Among the three different MWs, 40,000 Da DS was most effective in attenuating cell aggregation during the cultures of CS13‐1.00 cells, and showed the highest maximum mAb concentration. For SM‐0.025 cells, it significantly decreased specific mAb productivity, particularly at a high concentration of DS. Overall, DS addition did not negatively affect the quality attributes of mAbs (aggregation, charge variation, and glycosylation), though its efficacy on mAb quality depended on the MW and concentration of DS and cell lines. For both cell lines, the addition of DS did not affect N‐glycosylation of mAbs and decreased basic charge variants in mAbs. For CS13‐1.00 cells, the mAb monomer increased with the addition of 40,000 Da DS at 0.3–1.0 g/L. Taken together, to maximize the beneficial effect of DS addition on mAb production, the optimal MW and concentration of DS should be determined for each specific rCHO cell line. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1113–1122, 2016 相似文献
924.
Regulation,sensory domains and roles of two Desulfovibrio desulfuricans ATCC27774 Crp family transcription factors,HcpR1 and HcpR2, in response to nitrosative stress 下载免费PDF全文
925.
926.
Fuyang Li Gwanghyun Gwon Aera Jo Ae‐Kyoung Kim Taeyoon Kim Ok‐kyu Song Sang Eun Lee Yunje Cho 《The EMBO journal》2016,35(7):743-758
ATP‐dependent DNA end recognition and nucleolytic processing are central functions of the Mre11/Rad50 (MR) complex in DNA double‐strand break repair. However, it is still unclear how ATP binding and hydrolysis primes the MR function and regulates repair pathway choice in cells. Here, Methanococcus jannaschii MR‐ATPγS‐DNA structure reveals that the partly deformed DNA runs symmetrically across central groove between two ATPγS‐bound Rad50 nucleotide‐binding domains. Duplex DNA cannot access the Mre11 active site in the ATP‐free full‐length MR complex. ATP hydrolysis drives rotation of the nucleotide‐binding domain and induces the DNA melting so that the substrate DNA can access Mre11. Our findings suggest that the ATP hydrolysis‐driven conformational changes in both DNA and the MR complex coordinate the melting and endonuclease activity. 相似文献
927.
ATP‐driven Rad50 conformations regulate DNA tethering,end resection,and ATM checkpoint signaling 下载免费PDF全文
928.
Jose Bras Isabel Alonso Clara Barbot Maria?Manuela Costa Lee Darwent Tatiana Orme Jorge Sequeiros John Hardy Paula Coutinho Rita Guerreiro 《American journal of human genetics》2015,96(3):474-479
Hereditary autosomal-recessive cerebellar ataxias are a genetically and clinically heterogeneous group of disorders. We used homozygosity mapping and exome sequencing to study a cohort of nine Portuguese families who were identified during a nationwide, population-based, systematic survey as displaying a consistent phenotype of recessive ataxia with oculomotor apraxia (AOA). The integration of data from these analyses led to the identification of the same homozygous PNKP (polynucleotide kinase 3′-phosphatase) mutation, c.1123G>T (p.Gly375Trp), in three of the studied families. When analyzing this particular gene in the exome sequencing data from the remaining cohort, we identified homozygous or compound-heterozygous mutations in five other families. PNKP is a dual-function enzyme with a key role in different pathways of DNA-damage repair. Mutations in this gene have previously been associated with an autosomal-recessive syndrome characterized by microcephaly; early-onset, intractable seizures; and developmental delay (MCSZ). The finding of PNKP mutations associated with recessive AOA extends the phenotype associated with this gene and identifies a fourth locus that causes AOA. These data confirm that MCSZ and some forms of ataxia share etiological features, most likely reflecting the role of PNKP in DNA-repair mechanisms. 相似文献
929.
When cells undergo replication stress, proper checkpoint activation and deactivation are critical for genomic stability and cell survival and therefore must be highly regulated. Although mechanisms of checkpoint activation are well studied, mechanisms of checkpoint deactivation are far less understood. Previously, we reported that chromatin remodeling factors Isw2 and Ino80 attenuate the S-phase checkpoint activity in Saccharomyces cerevisiae, especially during recovery from hydroxyurea. In this study, we found that Isw2 and Ino80 have a more pronounced role in attenuating checkpoint activity during late S phase in the presence of methyl methanesulfonate (MMS). We therefore screened for checkpoint factors required for Isw2 and Ino80 checkpoint attenuation in the presence of MMS. Here we demonstrate that Isw2 and Ino80 antagonize checkpoint activators and attenuate checkpoint activity in S phase in MMS either through a currently unknown pathway or through RPA. Unexpectedly, we found that Isw2 and Ino80 increase chromatin accessibility around replicating regions in the presence of MMS through a novel mechanism. Furthermore, through growth assays, we provide additional evidence that Isw2 and Ino80 partially counteract checkpoint activators specifically in the presence of MMS. Based on these results, we propose that Isw2 and Ino80 attenuate S-phase checkpoint activity through a novel mechanism. 相似文献
930.