全文获取类型
收费全文 | 5336篇 |
免费 | 379篇 |
国内免费 | 2篇 |
专业分类
5717篇 |
出版年
2023年 | 32篇 |
2022年 | 63篇 |
2021年 | 138篇 |
2020年 | 62篇 |
2019年 | 94篇 |
2018年 | 121篇 |
2017年 | 95篇 |
2016年 | 178篇 |
2015年 | 182篇 |
2014年 | 249篇 |
2013年 | 323篇 |
2012年 | 348篇 |
2011年 | 340篇 |
2010年 | 197篇 |
2009年 | 189篇 |
2008年 | 227篇 |
2007年 | 244篇 |
2006年 | 192篇 |
2005年 | 196篇 |
2004年 | 164篇 |
2003年 | 138篇 |
2002年 | 150篇 |
2001年 | 140篇 |
2000年 | 123篇 |
1999年 | 99篇 |
1998年 | 44篇 |
1997年 | 42篇 |
1996年 | 34篇 |
1995年 | 42篇 |
1994年 | 40篇 |
1993年 | 29篇 |
1992年 | 89篇 |
1991年 | 69篇 |
1990年 | 87篇 |
1989年 | 70篇 |
1988年 | 80篇 |
1987年 | 74篇 |
1986年 | 72篇 |
1985年 | 68篇 |
1984年 | 56篇 |
1983年 | 33篇 |
1981年 | 27篇 |
1980年 | 36篇 |
1979年 | 45篇 |
1978年 | 31篇 |
1977年 | 35篇 |
1976年 | 34篇 |
1974年 | 31篇 |
1973年 | 33篇 |
1972年 | 31篇 |
排序方式: 共有5717条查询结果,搜索用时 0 毫秒
81.
82.
In this study, herpes simplex virus Type 2 (HSV-2)-transformed cells (H238) and conditioned medium (CM) from H238 cell cultures were studied with respect to their effects on lymphoproliferation and the chemiluminescent oxidative burst of phagocytic cells. The H238 cells expressed a nuclear antigen detectable by fluorescent antibody testing using pooled sera from tumor-bearing mice, but no HSV-1 or HSV-2 cell membrane antigens could be found using specific monoclonal antibodies. BALB/c mice subcutaneously injected with 1 X 10(6) H238 cells developed progressively growing fibrosarcomas and depressed T lymphocyte blastogenesis in response to phytohemagglutinin (PHA) by 6 weeks post-injection when compared to non-injected controls. In contrast, oxygen radical production was increased by nearly 28-fold in the tumor-bearing subjects at this time. Incubation of normal mouse spleen cells in 100 microliters to 500 microliters of CM/ml resulted in significant dose-dependent suppression of PHA-induced lymphoproliferation. This was seen when the total spleen cell population was used, as well as after removal of the adherent cells, thereby suggesting that the inhibitory effect was not due to activation of adherent suppressor cells by the CM. However, the oxidative burst of total and adherent spleen cells from normal mice was significantly enhanced by the presence of either the H238 cells or their CM. In contrast, oxygen radical production by J774A.1 cells (a BALB/c mouse macrophage cell line) was depressed by H238 cells. Our results show that H238 tumors can alter lymphocyte as well as phagocytic cell functions both in vivo and in vitro. These tumor-induced modulations may occur via secretion of soluble factors or direct cell-to-cell interactions and, thus, may influence the outcome of immunotherapy in the tumor-bearing host. 相似文献
83.
Young Jun Kim Kwang Pyo Kim Hae Jin Rhee Sudipto Das John D Rafter Youn Sang Oh Wonhwa Cho 《The Journal of biological chemistry》2002,277(11):9358-9365
Mammalian secretory phospholipases A(2) (sPLA(2)) have been implicated in cellular eicosanoid biosynthesis but the mechanism of their cellular action remains unknown. To elucidate the spatiotemporal dynamics of sPLA(2) mobilization and determine the site of its lipolytic action, we performed time-lapse confocal microscopic imaging of fluorescently labeled sPLA(2) acting on human embryonic kidney (HEK) 293 cells the membranes of which are labeled with a fluorogenic phospholipid, N-((6-(2,4-dinitrophenyl)amino)hexanoyl)-1-hexadecanoyl-2-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-sn-glycero-3-phosphoethanolamine. The Western blotting analysis of HEK293 cells treated with exogenous sPLA(2)s showed that not only the affinity for heparan sulfate proteoglycan but also other factors, such as sPLA(2) hydrolysis products or cytokines, are necessary for the internalization of sPLA(2) into HEK293 cells. Live cell imaging showed that the hydrolysis of fluorogenic phospholipids incorporated into HEK293 cell membranes was synchronized with the spatiotemporal dynamics of sPLA(2) internalization, detectable initially at the plasma membrane and then at the perinuclear region. Also, immunocytostaining showed that human group V sPLA(2) induced the translocation of 5-lipoxygenase to the nuclear envelope at which they were co-localized. Together, these studies provide the first experimental evidence that the internalized sPLA(2) acts on the nuclear envelope to provide arachidonate for other enzymes involved in the eicosanoid biosynthesis. 相似文献
84.
Sharma Shivani Kumar Amit Dhakte Priyanka Raturi Gaurav Vishwakarma Gautam Barbadikar Kalyani M. Das B. K. Shivaraj S. M. Sonah Humira Deshmukh Rupesh 《Journal of Plant Growth Regulation》2023,42(1):46-59
Journal of Plant Growth Regulation - Crop improvement in light of the rapidly changing climate and the increasing human population continues to be one of the primary concerns for researchers across... 相似文献
85.
The mechanism of protein synthesis is still unknown due to inability to detect the so-called enzyme "peptidyl transferase" even after elucidation of high-resolution crystal structure of ribosome. We have recently shown by model building and semi-empirical energy calculation that the tRNA molecule at P-site of ribosome may act as peptidyl transferase (Das et al. (1999) J. Theor. Biol. 200, 193-205). We proposed that the tetrahedral intermediate formed from nucleophylic attack of CO of P-site amino-acylated tRNA by NH2 of A-site amino-acylated tRNA is converted to a six-member ring intermediate by conformational change. This ring intermediate produces a free tRNA and a tRNA covalently linked to a peptide. However, energy of the six-member ring intermediate was calculated to be quite high. We show here that the energy values of all the reactants, intermediates and products are within the expected range when they are calculated using high level ab initio quantum chemical methods. 相似文献
86.
87.
Dwivedi VP Tousif S Bhattacharya D Prasad DV Van Kaer L Das J Das G 《The Journal of biological chemistry》2012,287(5):2943-2947
TGF-β is a pleiotropic cytokine that predominantly exerts inhibitory functions in the immune system. Unexpectedly, the in vitro differentiation of both Th17 and Tc17 cells requires TGF-β. However, animals that are impaired in TGF-β signaling (TGF-βRIIDN mice) display multiorgan autoimmune disorders. Here we show that CD4(+) T cells from TGF-βRIIDN mice are resistant to Th17 cell differentiation and, paradoxically, that CD8(+) T cells from these animals spontaneously acquire an IL-17-producing phenotype. Neutralization of IL-17 or depletion of CD8(+) T cells dramatically inhibited inflammation in TGF-βRIIDN mice. Therefore, the absence of TGF-β triggers spontaneous differentiation of IL-17-producing CD8(+) T cells, suggesting that the in vivo and in vitro conditions that promote the differentiation of IL-17-producing CD8(+) T cells are distinct. 相似文献
88.
89.
Pangkhi Medhi Ololade Olatunji Atul Nayak Chandra Teja Uppuluri Richard T. Olsson Buchi N. Nalluri Diganta B. Das 《AAPS PharmSciTech》2017,18(5):1488-1494
Microneedle (MN) technology has emerged as an effective drug delivery system, and it has tremendous potential as a patient friendly substitute for conventional methods for transdermal drug delivery (TDD). In this paper, we report on the preparation of lidocaine-loaded biodegradable microneedles, which are manufactured from fish scale-derived collagen. Lidocaine, a common tissue numbing anaesthetic, is loaded in these microneedles with an aim of delivering the drug with controlled skin permeation. Evaluation of lidocaine permeation in porcine skin has been successfully performed using Franz diffusion cell (FDC) which has shown that the drug permeation rate increases from 2.5 to 7.5% w/w after 36 h and pseudo steady state profile is observed from 5.0 to 10.0% w/w lidocaine-loaded microneedle. Swelling experiments have suggested that the microneedles have negligible swellability which implies that the patch would stick to the tissue when inserted. The experiments on MN dissolution have depicted that the lidocaine loaded in the patch is lower than the theoretical loading, which is expected as there can be losses of the drug during initial process manufacture. 相似文献
90.
Liu L Lanner F Lendahl U Das D 《Biochemical and biophysical research communications》2011,(3):426-431
Numb serves as a key regulator of Notch and Sonic Hedgehog signaling and also modulates p53 protein levels. Numblike is a highly conserved homolog to mammalian Numb, but considerably less is known about its function. To address the role of Numblike, we have generated a mouse embryonic stem (ES) cell line, NblTetOn, in which expression of Numblike can be induced and analyzed the effect of activation of Numblike. Induction of Numblike, similar to Numb, reduced the amount of Notch receptor, whereas Numblike differed from Numb with regard to p53 and Shh signaling. In contrast to Numb, Numblike did not elevate the level of p53 protein and Numblike potentiated, rather than reduced, the immediate downstream response of Shh signaling. In keeping with a role for Numblike in potentiating Shh signaling, Shh and Numblike synergistically increased the proportion of ES cells expressing pluripotency markers. In conclusion, the data demonstrate that Numb and Numblike have evolved to acquire at least partially distinct functions. 相似文献