全文获取类型
收费全文 | 21900篇 |
免费 | 2123篇 |
国内免费 | 10篇 |
出版年
2021年 | 318篇 |
2020年 | 250篇 |
2019年 | 330篇 |
2018年 | 488篇 |
2017年 | 419篇 |
2016年 | 689篇 |
2015年 | 1049篇 |
2014年 | 1171篇 |
2013年 | 1397篇 |
2012年 | 1720篇 |
2011年 | 1635篇 |
2010年 | 1128篇 |
2009年 | 904篇 |
2008年 | 1293篇 |
2007年 | 1201篇 |
2006年 | 1065篇 |
2005年 | 971篇 |
2004年 | 979篇 |
2003年 | 795篇 |
2002年 | 721篇 |
2001年 | 422篇 |
2000年 | 391篇 |
1999年 | 320篇 |
1998年 | 189篇 |
1997年 | 165篇 |
1996年 | 128篇 |
1995年 | 139篇 |
1994年 | 144篇 |
1993年 | 124篇 |
1992年 | 202篇 |
1991年 | 217篇 |
1990年 | 186篇 |
1989年 | 198篇 |
1988年 | 180篇 |
1987年 | 163篇 |
1986年 | 161篇 |
1985年 | 151篇 |
1984年 | 126篇 |
1983年 | 98篇 |
1982年 | 99篇 |
1981年 | 101篇 |
1980年 | 95篇 |
1979年 | 114篇 |
1978年 | 106篇 |
1977年 | 70篇 |
1976年 | 88篇 |
1975年 | 98篇 |
1974年 | 97篇 |
1973年 | 89篇 |
1972年 | 70篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
1.
Jung Mi Lim Kyung S. Lee Hyun Ae Woo Dongmin Kang Sue Goo Rhee 《The Journal of cell biology》2015,210(1):935-945
Proteins associated with the centrosome play key roles in mitotic progression in mammalian cells. The activity of Cdk1-opposing phosphatases at the centrosome must be inhibited during early mitosis to prevent premature dephosphorylation of Cdh1—an activator of the ubiquitin ligase anaphase-promoting complex/cyclosome—and the consequent premature degradation of mitotic activators. In this paper, we show that reversible oxidative inactivation of centrosome-bound protein phosphatases such as Cdc14B by H2O2 is likely responsible for this inhibition. The intracellular concentration of H2O2 increases as the cell cycle progresses. Whereas the centrosome is shielded from H2O2 through its association with the H2O2-eliminating enzyme peroxiredoxin I (PrxI) during interphase, the centrosome-associated PrxI is selectively inactivated through phosphorylation by Cdk1 during early mitosis, thereby exposing the centrosome to H2O2 and facilitating inactivation of centrosome-bound phosphatases. Dephosphorylation of PrxI by okadaic acid–sensitive phosphatases during late mitosis again shields the centrosome from H2O2 and thereby allows the reactivation of Cdk1-opposing phosphatases at the organelle. 相似文献
2.
W. D. Roof H. Q. Fang K. D. Young Jianling Sun & Ry Young 《Molecular microbiology》1997,25(6):1031-1046
slyD encodes a 196 amino acid polypeptide that is a member of the FKBP family of cis–trans peptidyl–prolyl isomerases (PPIases). slyD mutations affect plaque formation by the phage φX174 by blocking the action of the phage lysis protein E. Here we describe the selection of a set of spontaneous slyD mutations conferring resistance to the expression of gene E from a plasmid. These mutations occur disproportionately in residues of SlyD that, based on the structure of the prototype mammalian FKBP12, make ligand contacts with immunosuppressing drug molecules or are conserved in other FKBP proteins. A wide variation in the plating efficiency of φX174 on these E R strains is observed, relative to the parental, indicating that these alleles differ widely in residual SlyD activity. Moreover, it is found that slyD mutations cause significant growth rate defects in Escherichia coli B and C backgrounds. Finally, overexpression of slyD causes filamentation of the host. Thus, among the FKBP genes found in organisms across the evolutionary spectrum, slyD is unique in having three distinct drug-independent phenotypes. 相似文献
3.
Molecular Biology Reports - We present here on an innovative assay for detecting miRNAs using a uniquely designed specific extension sequence that provides high efficiency and accuracy. This assay... 相似文献
4.
Pasupathi Sundaramoorthy Jae Jun Sim Yeong-Su Jang Siddhartha Kumar Mishra Keun-Yeong Jeong Poonam Mander Oh Byung Chul Won-Sik Shim Seung Hyun Oh Ky-Youb Nam Hwan Mook Kim 《PloS one》2015,10(1)
Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK) plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+) supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa), its downstream signaling and role in the motility of human colon cancer cells. We found that treating HCT116 and HT-29 cells with CaLa immediately increased the intracellular Ca2+ (iCa2+) levels for a prolonged period of time. Ca2+ influx induced cleavage of FAK into an N-terminal FAK (FERM domain) in a dose-dependent manner. Phosphorylated FAK (p-FAK) was also cleaved in to its p-N-terminal FAK. CaLa increased colon cancer cells motility. Calpeptin, a calpain inhibitor, reversed the effects of CaLa on FAK and pFAK cleavage in both cancer cell lines. The cleaved FAK translocates into the nucleus and modulates p53 stability through MDM2-associated ubiquitination. CaLa-induced Ca2+ influx increased the motility of colon cancer cells was mediated by calpain activity through FAK and pFAK protein destabilization. In conclusion, these results suggest that careful consideration may be given in deciding dietary Ca2+ supplementation to patient undergoing treatment for metastatic cancer. 相似文献
5.
Eun Jin Park Joon Young Song Min Ju Choi Ji Ho Jeon Jah-yeon Choi Tae Un Yang Kyung Wook Hong Ji Yun Noh Hee Jin Cheong Woo Joo Kim 《The Korean journal of parasitology》2014,52(4):425-428
A 45-year-old-male who had underlying ulcerative colitis and presented with fever and dry cough. Initially, the patient was considered to have invasive aspergillosis due to a positive galactomannan assay. He was treated with amphotericin B followed by voriconazole. Nevertheless, the patient deteriorated clinically and radiographically. The lung biopsy revealed eosinophilic pneumonia, and ELISA for Toxocara antigen was positive, leading to a diagnosis of pulmonary toxocariasis. After a 10-day treatment course with albendazole and adjunctive steroids, the patient recovered completely without any sequelae. Pulmonary toxocariasis may be considered in patients with subacute or chronic pneumonia unresponsive to antibiotic agents, particularly in cases with eosinophilia. 相似文献
6.
Fatty acyl-CoAs are potential in vivo inactivators of glucose-6-phosphate dehydrogenase (G6PD). Ovariectomized mature rats (n = 74) were given 5 micrograms of estradiol intravenously, then killed 0, 24, 36, 48 and 72 h later. Control levels of myristoyl-, palmitoyl-, stearoyl-, arachidonoyl-, oleoyl- and linoleoyl-CoA were 0.6, 3.2, 4.7, 3.4, 2.4 and 3.0 micrograms/uterus and were increased 39, 110, 146, 100, 84 and 69% at 36-48 h, respectively. Levels of fatty acyl-CoAs in the rat uterus become elevated 36 h after estradiol treatment. At the same time G6PD changes from a stable enzyme to one that is irreversibly inactivated, possibly due to being rapidly degraded. Progesterone (2 mg subcutaneously every 12 h, n = 30), administered beginning at either 24 or 36 h after estradiol treatment, had no effect on estradiol-induced changes in myristoyl-, palmitoyl-, or stearoyl-CoA. Compared to the groups of rats treated with estradiol alone, animals treated with combinations of estradiol and progesterone exhibited higher levels of arachidonoyl-CoA after 48 h, and oleoyl-CoA and linoleoyl-CoA were greater after 72 h. Progesterone increased the estradiol-induced levels of unsaturated fatty acyl-CoAs suggesting that progesterone may induce uterine fatty acid desaturase activity and/or uptake of dietary fatty acids. Addition of fatty acyl-CoAs, at concentrations seen in vivo at 36-48 h after estradiol, to purified G6PD, causes irreversible G6PD inactivation. 相似文献
7.
J. Young 《BMJ (Clinical research ed.)》1996,313(7058):677-681
Rehabilitation is concerned with lessening the impact of disabling conditions. These are particularly common in older people and considerable health gain can be achieved by successful rehabilitation. Hospital doctors and general practitioners should be aware of the core principles of rehabilitation, be able to recognise rehabilitation need in their patients, and have sufficient knowledge of their local rehabilitation services to trigger the referral process. 相似文献
8.
A serum- and glucocorticoid-regulated 4-kilobase mRNA encodes a cyclooxygenase-related protein. 总被引:21,自引:0,他引:21
M K O'Banion H B Sadowski V Winn D A Young 《The Journal of biological chemistry》1991,266(34):23261-23267
9.
So Jeong Park Doo Ri Park Deepak Bhattarai Kyeong Lee Jaesang Kim Yun Soo Bae Soo Young Lee 《Molecules and cells》2014,37(8):628-635
2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity. 相似文献
10.