全文获取类型
收费全文 | 5586篇 |
免费 | 618篇 |
国内免费 | 1篇 |
专业分类
6205篇 |
出版年
2023年 | 28篇 |
2022年 | 60篇 |
2021年 | 146篇 |
2020年 | 74篇 |
2019年 | 86篇 |
2018年 | 108篇 |
2017年 | 91篇 |
2016年 | 155篇 |
2015年 | 251篇 |
2014年 | 262篇 |
2013年 | 318篇 |
2012年 | 430篇 |
2011年 | 423篇 |
2010年 | 260篇 |
2009年 | 239篇 |
2008年 | 340篇 |
2007年 | 358篇 |
2006年 | 328篇 |
2005年 | 286篇 |
2004年 | 268篇 |
2003年 | 242篇 |
2002年 | 232篇 |
2001年 | 75篇 |
2000年 | 54篇 |
1999年 | 68篇 |
1998年 | 58篇 |
1997年 | 48篇 |
1996年 | 35篇 |
1995年 | 35篇 |
1994年 | 42篇 |
1993年 | 25篇 |
1992年 | 39篇 |
1991年 | 53篇 |
1990年 | 42篇 |
1989年 | 45篇 |
1988年 | 49篇 |
1987年 | 33篇 |
1986年 | 30篇 |
1985年 | 35篇 |
1983年 | 25篇 |
1982年 | 25篇 |
1981年 | 23篇 |
1980年 | 21篇 |
1979年 | 31篇 |
1978年 | 31篇 |
1977年 | 22篇 |
1973年 | 28篇 |
1972年 | 22篇 |
1971年 | 23篇 |
1970年 | 27篇 |
排序方式: 共有6205条查询结果,搜索用时 15 毫秒
1.
Minh C. Nguyen Guang Huan Tu Kathryn E. Koprivnikar Melissa Gonzalez-Edick Karin U. Jooss Thomas C. Harding 《Cancer immunology, immunotherapy : CII》2010,59(9):1313-1323
A critical factor in clinical development of cancer immunotherapies is the identification of tumor-associated antigens that
may be related to immunotherapy potency. In this study, protein microarrays containing >8,000 human proteins were screened
with serum from prostate cancer patients (N = 13) before and after treatment with a granulocyte–macrophage colony-stimulating factor (GM-CSF)-secreting whole cell immunotherapy.
Thirty-three proteins were identified that displayed significantly elevated (P ≤ 0.05) signals in post-treatment samples, including three proteins that have previously been associated with prostate carcinogenesis,
galectin-8, T-cell alternative reading frame protein (TARP) and TNF-receptor-associated protein 1 (TRAP1). Expanded analysis
of antibody induction in metastatic, castration-resistant prostate cancer (mCRPC) patients (N = 92) from two phase 1/2 trials of prostate cancer immunotherapy, G-9803 and G-0010, indicated a significant (P = 0.03) association of TARP antibody induction and median survival time (MST). Antibody induction to TARP was also significantly
correlated (P = 0.036) with an increase in prostate-specific antigen doubling time (PSADT) in patients with a biochemical (PSA) recurrence
following prostatectomy or radiation therapy (N = 19) from in a previous phase 1/2 trial of prostate cancer immunotherapy, G-9802. RNA and protein encoding TARP and TRAP1
was up-regulated in prostate cancer tissue compared to matched normal controls. These preliminary findings suggest that antibody
induction to TARP may represent a possible biomarker for treatment response to GM-CSF secreting cellular immunotherapy in
prostate cancer patients and demonstrates the utility of using protein microarrays for the high-throughput screening of patient-derived
antibody responses. 相似文献
2.
Gerald R.V. Hammond Matthias P. Machner Tamas Balla 《The Journal of cell biology》2014,205(1):113-126
Polyphosphoinositides are an important class of lipid that recruit specific effector proteins to organelle membranes. One member, phosphatidylinositol 4-phosphate (PtdIns4P) has been localized to Golgi membranes based on the distribution of lipid binding modules from PtdIns4P effector proteins. However, these probes may be biased by additional interactions with other Golgi-specific determinants. In this paper, we derive a new PtdIns4P biosensor using the PtdIns4P binding of SidM (P4M) domain of the secreted effector protein SidM from the bacterial pathogen Legionella pneumophila. PtdIns4P was necessary and sufficient for localization of P4M, which revealed pools of the lipid associated not only with the Golgi but also with the plasma membrane and Rab7-positive late endosomes/lysosomes. PtdIns4P distribution was determined by the localization and activities of both its anabolic and catabolic enzymes. Therefore, P4M reports a wider cellular distribution of PtdIns4P than previous probes and therefore will be valuable for dissecting the biological functions of PtdIns4P in its assorted membrane compartments. 相似文献
3.
Kathryn L. Butler Vijayakrishnan Ambravaneswaran Nitin Agrawal Maryelizabeth Bilodeau Mehmet Toner Ronald G. Tompkins Shawn Fagan Daniel Irimia 《PloS one》2010,5(7)
Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72–120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions. 相似文献
4.
5.
6.
Kathryn M. Denkowski George C. Denkowski 《Applied psychophysiology and biofeedback》1984,9(3):353-364
This study examined whether group progressive relaxation training was as effective as individual EMG biofeedback training in facilitating the academic achievement and self-control of 45 hyperactive elementary school children. Academic achievement was assessed with the Gates-MacGinities Reading Tests, and self-control was measured with the Nowicki-Strickland and the Teacher Rating scales. Eight sessions were scheduled at weekly intervals. Progressive relaxation was conducted in groups of seven or eight and was induced with a commercial audiocassette program. EMG training augmented frontalis biofeedback with those taped exercises. A placebo group listened to taped children's stories. Multivariate analysis of variance indicated no significant differences among the three contrast groups when all dependent variables were considered together. However, univariate F values and discriminant analysis disclosed locus of control to be significantly more internal for the progressive relaxation condition. Also, differences between the two relaxation and the placebo groups, though not statistically significant, were all in the expected direction. While the relative efficacy of group progressive relaxation could not be established conclusively, the data appeared sufficiently positive to warrant further investigation of this cost-effective prospective intervention.The opinions expressed by the authors are not necessarily those of their respective institutions. 相似文献
7.
8.
Vasant Chellappa Kendra N. Taylor Kathryn Pedrick Carlos Donado Ilka Arun Netravali Khaleda Haider Annaiah Cariappa Natasha F. Dalomba Shiv Pillai 《PloS one》2013,8(1)
Catalytically defective rare variants of Sialic acid Acetyl Esterase (SIAE) have previously been linked to autoimmunity. Studies presented here confirm that the M89V SIAE protein and all other products of common variant alleles of SIAE are catalytically normal. Although overexpressing transfected non-lymphoid cells secrete small amounts of SIAE that can associate with the cell surface, normal human lymphocytes do not exhibit cell surface SIAE, supporting genetic evidence in mice that indicates that this protein functions in a lymphocyte intrinsic manner. Analyses of the plasma proteome also indicate that SIAE is not secreted in vivo. A re-analysis exclusively of catalytically defective rare variant alleles of SIAE in subjects in which this gene was completely sequenced confirmed an association of SIAE with autoimmunity. A subset of catalytically defective rare variant SIAE alleles has previously been typed in a large genotyping study comparing a diverse group of disease subjects and controls; our re-analysis of this data shows that catalytically defective alleles are enriched in disease subjects. These data suggest that SIAE may be associated with autoimmunity and that further study of catalytically defective rare variant SIAE alleles in terms of autoimmune disease susceptibility is strongly warranted. 相似文献
9.
Expression of renal cell protein markers is dependent on initial mechanical culture conditions. 总被引:4,自引:0,他引:4
Nancy L Cowger Edmund Benes Patricia L Allen Timothy G Hammond 《Journal of applied physiology》2002,92(2):691-700
The rotating wall vessel is optimized for suspension culture, with laminar flow and adequate nutrient delivery, but minimal shear. However, higher shears may occur in vivo. During rotating wall vessel cultivation of human renal cells, size and density of glass-coated microcarrier beads were changed to modulate initial shear. Renal-specific proteins were assayed after 2 days. Flow cytometry antibody binding analysis of vitamin D receptor demonstrated peak expression at intermediate shears, with 30% reduction outside this range. Activity of cathepsin C showed the inverse pattern, lowest at midshear, with twofold increases at either extreme. Dipeptidyl-peptidase IV had no shear dependence, suggesting that the other results are specific, not universal, changes in membrane trafficking or protein synthesis. On addition of dextran, which changes medium density and viscosity but not shear, vitamin D receptor assay showed no differences from controls. Neither cell cycle, apoptosis/necrosis indexes, nor lactate dehydrogenase release varied between experiments, confirming that the changes are primary, not secondary to cell cycling or membrane damage. This study provides direct evidence that mechanical culture conditions modulate protein expression in suspension culture. 相似文献
10.