全文获取类型
收费全文 | 1859篇 |
免费 | 71篇 |
国内免费 | 316篇 |
专业分类
2246篇 |
出版年
2023年 | 4篇 |
2018年 | 10篇 |
2017年 | 7篇 |
2016年 | 5篇 |
2015年 | 13篇 |
2014年 | 32篇 |
2013年 | 37篇 |
2012年 | 99篇 |
2011年 | 131篇 |
2010年 | 23篇 |
2009年 | 10篇 |
2008年 | 161篇 |
2007年 | 149篇 |
2006年 | 123篇 |
2005年 | 207篇 |
2004年 | 153篇 |
2003年 | 128篇 |
2002年 | 138篇 |
2001年 | 135篇 |
2000年 | 151篇 |
1999年 | 84篇 |
1998年 | 30篇 |
1997年 | 13篇 |
1996年 | 24篇 |
1995年 | 30篇 |
1994年 | 18篇 |
1993年 | 8篇 |
1992年 | 4篇 |
1990年 | 7篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1959年 | 20篇 |
1958年 | 51篇 |
1957年 | 29篇 |
1956年 | 28篇 |
1955年 | 20篇 |
1954年 | 29篇 |
1953年 | 17篇 |
1952年 | 12篇 |
1951年 | 23篇 |
1950年 | 8篇 |
1949年 | 5篇 |
1948年 | 5篇 |
1947年 | 3篇 |
1945年 | 5篇 |
1934年 | 3篇 |
排序方式: 共有2246条查询结果,搜索用时 15 毫秒
961.
962.
Approximately 60,000 microorganisms from Saskatchewan soil were screened for growth on the cytokinin N6-benzyladenine (BA) as C source. A single isolate, identified as Serratia proteamaculans, grew well on BA. The culture filtrates from S. proteamaculans were screened using reversed phase high performance liquid chromatography (RP-HPLC) for the presence of secondary metabolites. The analysis revealed a major metabolite and its chemical structure was deduced as 8-hydroxy-N6-benzyladenine (8-OHBA). Subsequently, the S. proteamaculans isolate was also found to metabolize N6-(2-isopentenyl)adenine and adenine through oxidation of C-8 of the purine ring. A clone of the S. proteamaculans xanthine dehydrogenase (Xdh, EC 1.1.1.204) encoding genes was isolated in Escherichia coli. This E. coli isolate metabolized BA to 8-OHBA. Similar to other bacterial Xdh, the S. proteamaculans enzyme was composed of two subunits. The derived amino acid sequences of these Xdh subunits were most similar (XdhA, 60%; XdhB, 72%) to those of Pseudomonas aeruginosa. 相似文献
963.
Tauopathies are characterized by abnormal aggregation of the microtubule associated protein tau. This aggregation is thought to occur when tau undergoes shifts from its native conformation to one that exposes hydrophobic areas on separate monomers, allowing contact and subsequent association into oligomers and filaments. Molecular chaperones normally function by binding to exposed hydrophobic stretches on proteins and assisting in their refolding. Chaperones of the heat shock protein 70 (Hsp70) family have been implicated in the prevention of abnormal tau aggregation in adult neurons. Tau exists as six alternatively spliced isoforms, and all six isoforms appear capable of forming the pathological aggregates seen in Alzheimer's disease. Because tau isoforms differ in primary sequence, we sought to determine whether Hsp70 would differentially affect the aggregation and microtubule assembly characteristics of the various tau isoforms. We found that Hsp70 inhibits tau aggregation directly and not through inducer-mediated effects. We also determined that Hsp70 inhibits the aggregation of each individual tau isoform and was more effective at inhibiting the three repeat isoforms. Finally, all tau isoforms robustly induced microtubule formation while in the presence of Hsp70. The results presented herein indicate that Hsp70 affects tau isoform dysfunction while having very little impact on the normal function of tau to mediate microtubule assembly. This indicates that targeting Hsp70 to tau may provide a therapeutic approach for the treatment of tauopathies that avoids disruption of normal tau function. 相似文献
964.
Lezcano V Bellido T Plotkin LI Boland R Morelli S 《Archives of biochemistry and biophysics》2012,518(2):95-102
Bisphosphonates (BPs) inhibit osteocyte and osteoblast apoptosis via opening of connexin (Cx) 43 hemichannels and activating the extracellular signal regulated kinases ERKs. Previously, we hypothesized that intracellular survival signaling is initiated by interaction of BPs with Cx43. However, using whole cell binding assays with [(3)H]-alendronate, herein we demonstrated the presence of saturable, specific and high affinity binding sites in the Cx43-expressing ROS 17/2.8 osteoblastic cells, authentic osteoblasts and MLO-Y4 cells expressing Cx43 or not, as well as in HeLa cells lacking Cx43 expression and ROS 17/2.8 cells pretreated with agents that disassemble Cx channels. In addition, both BPs and the PTP inhibitor Na(3)VO(4) increased proliferation of cells expressing Cx43 or not. Furthermore, although BPs are internalized and inhibit intracellular enzymes in osteoclasts, whether the drugs penetrate non-resorptive bone cells is not known. To clarify this, we evaluated the osteoblastic uptake of AF-ALN, a fluorescently labeled analog of alendronate. AF-ALN was rapidly internalized in cells expressing Cx43 or not indicating that this process is not mediated via Cx43 hemichannels. Altogether, these findings suggest that although required for triggering intracellular survival signaling by BPs, Cx43 is dispensable for cellular BP binding, its uptake, as well as the proliferative effects of these agents. 相似文献
965.
Tep C Kim ML Opincariu LI Limpert AS Chan JR Appel B Carter BD Yoon SO 《The Journal of biological chemistry》2012,287(2):1600-1608
Brain-derived neurotrophic factor (BDNF) was shown to play a role in Schwann cell myelination by recruiting Par3 to the axon-glial interface, but the underlying mechanism has remained unclear. Here we report that Par3 regulates Rac1 activation by BDNF but not by NRG1-Type III in Schwann cells, although both ligands activate Rac1 in vivo. During development, active Rac1 signaling is localized to the axon-glial interface in Schwann cells by a Par3-dependent polarization mechanism. Knockdown of p75 and Par3 individually inhibits Rac1 activation, whereas constitutive activation of Rac1 disturbs the polarized activation of Rac1 in vivo. Polarized Rac1 activation is necessary for myelination as Par3 knockdown attenuates myelination in mouse sciatic nerves as well as in zebrafish. Specifically, Par3 knockdown in zebrafish disrupts proper alignment between the axon and Schwann cells without perturbing Schwann cell migration, suggesting that localized Rac1 activation at the axon-glial interface helps identify the initial wrapping sites. We therefore conclude that polarization of Rac1 activation is critical for myelination. 相似文献
966.
967.
周汝滨 李永全 潘超仁 郑克勤 廖霞 陈小萍ZHOU Ru-bin LI Yong-quan PAN Chao-ren ZHENG Ke-qin LIAO Xia CHEN Xiao-ping 《遗传》1998,20(5):34-35
本文对来我室咨询的135例无精症患者进行了细胞遗传学分析,发现异常核型38例,其中47.XXY,t(6;9)(p21;p22)为世界首报核型。本文对异常核型与无精症之间的关系进行探讨。
Abstract:Cytogenetic studies have been done on 135 cases with azoospermia,and 38 cases of abnormal karyotypes were discovered.Among which,one abnormal karyotype was the first reported in the world.It is 47,XXY,t(6;9)(p21;q22).The relationship between abnormal karyotypes and azoospermia is discussed. 相似文献
968.
LI Zhengyu ZHAO Xia & WEI Yuquan . Department of Gynecology Obstetrics West China Second Hospital of Sichuan University Chengdu China . Key Laboratory of Biotherapy of Human Diseases of Ministry of Education West China Hospital of Sichuan university Chengdu China 《中国科学:生命科学英文版》2004,47(2):107-114
With progressing recognition of apoptosis in bio-logical and medical sciences, the apoptotic signal transduction has rapidly become a dominant project to reveal the molecular mechanisms of apoptotic process. A lot of researches about apoptotic signal transduction have showed the expression of heat shock proteins was closely correlated with cell growth and differen-tiation, and involved in the regulation of apoptosis in different signal transduction pathways. Here we re-view the effects of hsps… 相似文献
969.
Krieger IV Revina LP Kostina LI Buzdin AA Zalunin IA Chestukhina GG Stepanov VM 《Biochemistry. Biokhimii?a》1999,64(10):1163-1168
Proteins of molecular weight 65 and 62 kD and having affinity for toxins Cry4B and Cry11A produced by Bacillus thuringiensis ssp. israelensis have been isolated from brush border membranes of Aedes aegypti larvae using affinity chromatography. Using a ligand blotting technique, we show that the binding of these proteins to the biotinylated toxins is reversible and that the two toxins compete for binding to the two proteins. These proteins are likely to be Cry4B and Cry11A toxin receptors in gut epithelial cells of Aedes aegypti larvae. 相似文献
970.
Koba S Gao Z Xing J Sinoway LI Li J 《American journal of physiology. Heart and circulatory physiology》2006,291(6):H2735-H2742
In congestive heart failure (CHF), exaggerated sympathetic activation is observed during exercise, which elicits excess peripheral vasoconstriction. The mechanisms causing this abnormality are not fully understood. Central command is a central neural process that induces parallel activation of motor and cardiovascular systems. This study was undertaken to determine whether central command serves as a mechanism that contributes to the exaggerated sympathetic response to exercise in CHF. In decerebrated rats, renal and lumbar sympathetic nerve responses (RSNA and LSNA, respectively) to 30 s of fictive locomotion were examined. The fictive locomotion was induced by electrical stimulation of the mesencephalic locomotor region (MLR). The study was performed in control animals (fractional shortening > 40%) and animals with myocardial infarctions (MI; fractional shortening < 30%). With low stimulation of the MLR (current intensity = 20 microA), the sympathetic responses were not significantly different in the control (RSNA: +18 +/- 4%; LSNA: +3 +/- 2%) and MI rats (RSNA: +16 +/- 5%; LSNA: +8 +/- 3%). With intense stimulation of the MLR (50 microA), the responses were significantly greater in MI rats (RSNA: +127 +/- 15%; LSNA: +57 +/- 10%) than in the control rats (RSNA: +62 +/- 5%; LSNA: +21 +/- 6%). In this study, the data demonstrate that RSNA and LSNA responses to intense stimulation of the MLR are exaggerated in MI rats. We suggest that intense activation of central command may play a role in evoking exaggerated sympathetic activation and inducing excessive peripheral vasoconstriction during exercise in CHF. 相似文献