全文获取类型
收费全文 | 2367篇 |
免费 | 98篇 |
专业分类
2465篇 |
出版年
2024年 | 6篇 |
2023年 | 7篇 |
2022年 | 37篇 |
2021年 | 63篇 |
2020年 | 38篇 |
2019年 | 39篇 |
2018年 | 50篇 |
2017年 | 53篇 |
2016年 | 71篇 |
2015年 | 84篇 |
2014年 | 136篇 |
2013年 | 167篇 |
2012年 | 210篇 |
2011年 | 201篇 |
2010年 | 108篇 |
2009年 | 96篇 |
2008年 | 127篇 |
2007年 | 126篇 |
2006年 | 139篇 |
2005年 | 93篇 |
2004年 | 92篇 |
2003年 | 93篇 |
2002年 | 83篇 |
2001年 | 16篇 |
2000年 | 13篇 |
1999年 | 11篇 |
1998年 | 26篇 |
1997年 | 13篇 |
1996年 | 5篇 |
1995年 | 14篇 |
1994年 | 10篇 |
1993年 | 13篇 |
1992年 | 21篇 |
1991年 | 23篇 |
1990年 | 9篇 |
1989年 | 16篇 |
1988年 | 13篇 |
1987年 | 14篇 |
1985年 | 10篇 |
1984年 | 14篇 |
1983年 | 5篇 |
1982年 | 10篇 |
1980年 | 10篇 |
1979年 | 12篇 |
1978年 | 6篇 |
1977年 | 14篇 |
1975年 | 8篇 |
1973年 | 8篇 |
1972年 | 5篇 |
1970年 | 5篇 |
排序方式: 共有2465条查询结果,搜索用时 15 毫秒
241.
Preparation of chiral gamma-substituted-gamma-lactones (1) through kinetic resolution is described. (S)-(-)-1-Phenylethylamine (2) in the presence of anhydrous AlCl(3) shows satisfactory levels of enantioselection in reaction with racemic gamma-substituted-gamma-lactones 1, where (R)-1 remains unreacted, while (S)-1 is enantioselectively converted to the ring-opened amide (S,S)-4. The enantiopurity of (R)-(+)- gamma-substituted gamma-lactones recovered ranges from 62-98% ee. 相似文献
242.
The eccentric connectivity index, which has recently been employed successfully for the development of numerous mathematical models for the prediction of biological activities of diverse nature, has been reformed to overcome its limitations caused by degeneracy and insensitivity towards heteroatoms. The reformed eccentric connectivity index, termed the eccentric connectivity topochemical index, overcomes the limitations of the eccentric connectivity index by exhibiting very low degeneracy and displaying sensitivity to both the presence and relative position of heteroatoms without compromizing the discriminating power of the eccentric connectivity index. The relationship of the eccentric connectivity topochemical index, eccentric connectivity index and Wieners index with regard to the anti-HIV activity of 2, 3-diaryl-1, 3-thiazolidin-4-one derivatives was subsequently investigated. The values of the eccentric connectivity topochemical index, the eccentric connectivity index and Wieners index of each of 31 analogues comprizing the data set were computed using in-house computer program. Resultant data was analyzed and suitable models developed after identification of active ranges. Subsequently, each derivative was assigned a biological activity using these models, which was then compared with the reported anti-HIV activity. The accuracy of prediction using these models was found to vary from 81 to 90%. The proposed index offers a vast potential for virtual screening of combinatorial libraries, structure property/activity studies and drug design.Figure Basic structure of 2,3-diaryl-1, 3-thiazoidin-4-ones. 相似文献
243.
Synthesis and in vitro testing of J591 antibody-dendrimer conjugates for targeted prostate cancer therapy 总被引:5,自引:0,他引:5
Targeted therapeutics using antibodies are an attractive option over conventional cancer chemotherapeutics due to their potential to deliver a therapeutic specifically to cancer tissue without damaging normal tissue. However, there are known problems with immunoconjugates such as decreased immunoreactivity and poor solubility. Using dendrimers as carriers for these agents has the potential to resolve these issues. We synthesized J591 anti-PSMA (prostate specific membrane antigen) antibody dendrimer conjugates containing fluorophores on the dendrimer. The in vitro studies of these conjugates show that they specifically bind to cells expressing PSMA. Confocal microscopy experiments document the binding and internalization of these conjugates. This research encourages the further study of antibody-dendrimer-drug conjugates for use in targeted therapeutics. 相似文献
244.
B cells activated by lipopolysaccharide,but not by anti-Ig and anti-CD40 antibody,induce anergy in CD8+ T cells: role of TGF-beta 1 总被引:1,自引:0,他引:1
Parekh VV Prasad DV Banerjee PP Joshi BN Kumar A Mishra GC 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(12):5897-5911
B cells recognize Ag through their surface IgRs and present it in the context of MHC class II molecules to CD4(+) T cells. Recent evidence indicates that B cells also present exogenous Ags in the context of MHC class I to CD8(+) T cells and thus may play an important role in the modulation of CTL responses. However, in this regard, conflicting reports are available. One group of studies suggests that the interaction between B cells and CD8(+) T cells leads to the activation of the T cells, whereas other studies propose that it induces T cell tolerance. For discerning this dichotomy, we used B cells that were activated with either LPS or anti-Ig plus anti-CD40 Ab, which mimic the T-independent and T-dependent modes of B cell activation, respectively, to provide accessory signals to resting CD8(+) T cells. Our results show that, in comparison with anti-Ig plus anti-CD40 Ab-activated B cells, the LPS-activated B cells (LPS-B) failed to induce significant levels of proliferation, cytokine secretion, and cytotoxic ability of CD8(+) T cells. This hyporesponsiveness of CD8(+) T cells activated with LPS-B was significantly rescued by anti-TGF-beta1 Ab. Moreover, it was found that such hyporesponsive CD8(+) T cells activated with LPS-B had entered a state of anergy. Furthermore, LPS-B expresses a significantly higher level of TGF-beta1 on the surface, which caused the observed hyporesponsiveness of CD8(+) T cells. Therefore, this study, for the first time, provides a novel mechanism of B cell surface TGF-beta1-mediated hyporesponsiveness leading to anergy of CD8(+) T cells. 相似文献
245.
Sudarslal S Majumdar S Ramasamy P Dhawan R Pal PP Ramaswami M Lala AK Sikdar SK Sarma SP Krishnan KS Balaram P 《FEBS letters》2003,553(1-2):209-212
A 26 residue peptide (Am 2766) with the sequence CKQAGESCDIFSQNCCVG-TCAFICIE-NH(2) has been isolated and purified from the venom of the molluscivorous snail, Conus amadis, collected off the southeastern coast of India. Chemical modification and mass spectrometric studies establish that Am 2766 has three disulfide bridges. C-terminal amidation has been demonstrated by mass measurements on the C-terminal fragments obtained by proteolysis. Sequence alignments establish that Am 2766 belongs to the delta-conotoxin family. Am 2766 inhibits the decay of the sodium current in brain rNav1.2a voltage-gated Na(+) channel, stably expressed in Chinese hamster ovary cells. Unlike delta-conotoxins have previously been isolated from molluscivorous snails, Am 2766 inhibits inactivation of mammalian sodium channels. 相似文献
246.
247.
Pathak R Pant CS Shaw AK Bhaduri AP Gaikwad AN Sinha S Srivastava A Srivastava KK Chaturvedi V Srivastava R Srivastava BS 《Bioorganic & medicinal chemistry》2002,10(10):3187-3196
A series of acyclic deoxy carbohydrate derivatives from easily available carbohydrate enals 1, 2, 3 or 5 were prepared involving the Baylis-Hillman reaction. These newly formed carbohydrate based Baylis-Hillman adducts and their amino derivatives were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis H(37)R(v). Among the compounds evaluated for their antimycobacterial activity, compound (10) showed the desired activity in the range of 3.125 microg/mL. 相似文献
248.
Amoebocyte is the single type of cell circulating in the horseshoe crab hemolymph, which plays a major role in the defense system of the animal. Granules present in these cells are sensitive to nanogram quantities of bacterial endotoxins, which form the basis of the Limulus amoebocyte lysate (LAL) test. Normally, amoebocytes for the production of the LAL are collected by cardiac puncture; hence, development of the in vitro culture system for amoebocytes will reduce the variability of the lysate and help to conserve the 400 million-yr-old living fossil. In the present investigation we have attempted organ culture of gill flaps that have been shown to be the source of amoebocytes. The gill flaps were cultured at 28 degrees C on a rocker platform in a modified L-15 medium supplemented with 10% v/v horseshoe crab serum. This led to the release of amoebocytes outside the gill flaps for a period of 6-8 wk with a more or less steady number of amoebocytes during the weekly harvest. No significant difference was seen in the yield of amoebocytes from male and female horseshoe crabs. Confocal laser microscopy studies revealed significant difference in the size of amoebocytes released in vitro as compared with those obtained in vivo. Thus, we have optimized the culture conditions for the long-term generation of amoebocytes in vitro from the Indian horseshoe crab Tachypleus gigas by reducing the incidence of contamination, simulating in vivo conditions for the organ culture of gill flaps, and improvising the nutritional status using the modified L-15 medium, providing the desired osmolarity and pH. 相似文献
249.
Sharma R Srivastava S Bajpai VK Balapure AK 《In vitro cellular & developmental biology. Animal》2002,38(5):293-297
A repertoire of hormonal signals including estrogen regulate the growth, differentiation, and functioning of diverse target tissues, including the ovary, the mammary gland, and skeletal tissue. A serum-free culture system derived from rabbit endometrium explants has been devised and is reported here to explore estrogen action in vitro. The system involves aseptically harvesting the uterus from a virgin rabbit, dissecting the endometrium, explanting it into 1- to 2-mm(3) pieces weighing approximately 1-2 mg each, and incubating these pieces in serum-free Medium-199. The culture is carried out for a period of 4 d in a humidified CO(2) incubator at 37 degrees C with 5% CO(2). The effect of extraneously added estrogen (1 microg/ml) was investigated by histological and ultrastructural procedures. It was observed that estrogen could induce specific changes, such as abundant mitochondria, rough endoplasmic reticulum, golgi complex, and intracellular collagen deposition, in both the epithelial and the fibroblast cell components of the explanted tissue. The study, therefore, indicates that the proposed system is an ideal tool for exploring and demonstrating estrogen responsiveness under in vitro conditions. 相似文献
250.